VCV000438165.4 - ClinVar

NM_001379270.1(CNGA1):c.1666C>T (p.Arg556Ter)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001379270.1(CNGA1):c.1666C>T (p.Arg556Ter)

Variation ID: 438165 Accession: VCV000438165.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 4p12 4: 47936816 (GRCh38) [ NCBI UCSC ] 4: 47938833 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Sep 9, 2017	Feb 14, 2024	Jun 20, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_001379270.1:c.1666C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001366199.1:p.Arg556Ter	nonsense
NM_000087.5:c.1666C>T	NP_000078.3:p.Arg556Ter	nonsense
NM_001142564.2:c.1666C>T	NP_001136036.2:p.Arg556Ter	nonsense
NC_000004.12:g.47936816G>A
NC_000004.11:g.47938833G>A
NG_009193.1:g.81129C>T

... more HGVS ... less HGVS

Protein change

R629*, R556*

Other names

Canonical SPDI

NC_000004.12:47936815:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00003

Links

ClinGen: CA2911032 dbSNP: rs567961453 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CNGA1		-	-	GRCh38 GRCh37	13	498
LOC101927157	-	-	-	GRCh38	-	466

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Retinitis pigmentosa	Pathogenic (1)	no assertion criteria provided	Jan 1, 2015	RCV000504735.1
not provided	Pathogenic (1)	criteria provided, single submitter	Jun 20, 2022	RCV001857216.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jun 20, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002238245.3 First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024	Publications: PubMed (1) PubMed: 25611614 Comment: For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CNGA1 protein in which other variant(s) (p.Tyr648) have … (more) For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CNGA1 protein in which other variant(s) (p.Tyr648) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 438165). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 25611614). This variant is present in population databases (rs567961453, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Arg560*) in the CNGA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 131 amino acid(s) of the CNGA1 protein. (less)
Pathogenic (Jan 01, 2015)	no assertion criteria provided Method: research	Retinitis pigmentosa Affected status: yes Allele origin: unknown	NIHR Bioresource Rare Diseases, University of Cambridge Accession: SCV000599104.1 First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017	Publications: PubMed (2) PubMed: 28041643‚ 25611614 Observation 1: Number of individuals with the variant: 1 Sex: male Ethnicity/Population group: European Observation 2: Number of individuals with the variant: 1 Sex: female Ethnicity/Population group: European

Comment:

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CNGA1 protein in which other variant(s) (p.Tyr648*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 438165). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 25611614). This variant is present in population databases (rs567961453, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Arg560*) in the CNGA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 131 amino acid(s) of the CNGA1 protein.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Molecular genetic testing in clinical diagnostic assessments that demonstrate correlations in patients with autosomal recessive inherited retinal dystrophy.	Liu X	JAMA ophthalmology	2015	PMID: 25611614

Text-mined citations for rs567961453 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001379270.1(CNGA1):c.1666C>T (p.Arg556Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs567961453 ...