NM_000965.5(RARB):c.1220T>C (p.Leu407Pro) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 27, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004673873.1

Allele description [Variation Report for NM_000965.5(RARB):c.1220T>C (p.Leu407Pro)]

NM_000965.5(RARB):c.1220T>C (p.Leu407Pro)

Gene:

RARB:retinoic acid receptor beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p24.2

Genomic location:

Preferred name:

NM_000965.5(RARB):c.1220T>C (p.Leu407Pro)

HGVS:

NC_000003.12:g.25596489T>C
NG_029013.3:g.772167T>C
NG_052961.1:g.72884A>G
NM_000965.3:c.1220T>C
NM_000965.5:c.1220T>CMANE SELECT
NM_001290216.3:c.1241T>C
NM_001290217.2:c.884T>C
NM_001290266.2:c.1073T>C
NM_001290276.2:c.884T>C
NM_001290277.1:c.1082T>C
NM_001290300.2:c.1091T>C
NM_016152.4:c.884T>C
NP_000956.2:p.Leu407Pro
NP_001277145.1:p.Leu414Pro
NP_001277146.1:p.Leu295Pro
NP_001277195.1:p.Leu358Pro
NP_001277205.1:p.Leu295Pro
NP_001277206.1:p.Leu361Pro
NP_001277229.1:p.Leu364Pro
NP_057236.1:p.Leu295Pro
NC_000003.11:g.25637980T>C
NM_000965.4:c.1220T>C
NR_110892.2:n.1528T>C
NR_110893.2:n.1484T>C

Protein change:

L295P

Molecular consequence:

NM_000965.5:c.1220T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001290216.3:c.1241T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001290217.2:c.884T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001290266.2:c.1073T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001290276.2:c.884T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001290277.1:c.1082T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001290300.2:c.1091T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_016152.4:c.884T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_110892.2:n.1528T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110893.2:n.1484T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005163103	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 27, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005163103

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 27, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta.

Caron V, Chassaing N, Ragge N, Boschann F, Ngu AM, Meloche E, Chorfi S, Lakhani SA, Ji W, Steiner L, Marcadier J, Jansen PR, van de Pol LA, van Hagen JM, Russi AS, Le Guyader G, Nordenskjöld M, Nordgren A, Anderlid BM, Plaisancié J, Stoltenburg C, Horn D, et al.

Genet Med. 2023 Aug;25(8):100856. doi: 10.1016/j.gim.2023.100856. Epub 2023 Apr 20.

PubMed [citation]

PMID:: 37092537
PMCID:: PMC10757562

Details of each submission

From Ambry Genetics, SCV005163103.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The c.1220T>C (p.L407P) alteration is located in exon 8 (coding exon 8) of the RARB gene. This alteration results from a T to C substitution at nucleotide position 1220, causing the leucine (L) at amino acid position 407 to be replaced by a proline (P). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In an assay testing RARB function, this variant showed a functionally abnormal result (Caron, 2023). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 11, 2024

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