NM_000057.4(BLM):c.3613G>A (p.Val1205Ile) AND not specified

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Mar 5, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000120230.7

Allele description [Variation Report for NM_000057.4(BLM):c.3613G>A (p.Val1205Ile)]

NM_000057.4(BLM):c.3613G>A (p.Val1205Ile)

Gene:

BLM:BLM RecQ like helicase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_000057.4(BLM):c.3613G>A (p.Val1205Ile)

HGVS:

NC_000015.10:g.90804221G>A
NG_007272.1:g.91850G>A
NM_000057.4:c.3613G>AMANE SELECT
NM_001287246.2:c.3613G>A
NM_001287247.2:c.3359-4916G>A
NM_001287248.2:c.2488G>A
NP_000048.1:p.Val1205Ile
NP_001274175.1:p.Val1205Ile
NP_001274177.1:p.Val830Ile
LRG_20t1:c.3613G>A
LRG_20:g.91850G>A
NC_000015.9:g.91347451G>A
NM_000057.2:c.3613G>A
NM_000057.3:c.3613G>A
P54132:p.Val1205Ile

Protein change:

V1205I

Links:

UniProtKB: P54132#VAR_022299; dbSNP: rs28385141

NCBI 1000 Genomes Browser:

rs28385141

Molecular consequence:

NM_001287247.2:c.3359-4916G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000057.4:c.3613G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287246.2:c.3613G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287248.2:c.2488G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000084377	ITMI	no classification provided	not provided	germline	reference population	PubMed (1) [See all records that cite this PMID]
SCV000916683	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Jul 13, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23129629, 24728327 Citation Link,
SCV002071164	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Mar 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000084377

ITMI

no classification provided

not provided

germline

reference population

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

SCV000916683

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(Jul 13, 2018)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002071164

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Mar 5, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
African	germline	unknown	not provided	not provided	not provided	43	not provided	reference population
African_European	germline	unknown	not provided	not provided	not provided	46	not provided	reference population
Central_Asian	germline	unknown	not provided	not provided	not provided	50	not provided	reference population
East_Asian	germline	unknown	not provided	not provided	not provided	62	not provided	reference population
European	germline	unknown	not provided	not provided	not provided	331	not provided	reference population
Hispanic	germline	unknown	not provided	not provided	not provided	118	not provided	reference population
Whole_cohort	germline	unknown	not provided	not provided	not provided	681	not provided	reference population

Citations

PubMed

Non-Bloom syndrome-associated partial and total loss-of-function variants of BLM helicase.

Mirzaei H, Schmidt KH.

Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19357-62. doi: 10.1073/pnas.1210304109. Epub 2012 Nov 5.

PubMed [citation]

PMID:: 23129629
PMCID:: PMC3511070

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]

PMID:: 24728327
PMCID:: PMC3984285

See all PubMed Citations (3)

Details of each submission

From ITMI, SCV000084377.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	African	not provided	not provided	not provided	reference population	PubMed (1)
2	African_European	not provided	not provided	not provided	reference population	PubMed (1)
3	Central_Asian	not provided	not provided	not provided	reference population	PubMed (1)
4	East_Asian	not provided	not provided	not provided	reference population	PubMed (1)
5	European	not provided	not provided	not provided	reference population	PubMed (1)
6	Hispanic	not provided	not provided	not provided	reference population	PubMed (1)
7	Whole_cohort	not provided	not provided	not provided	reference population	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	43	not provided	discovery		not provided	0.0116	not provided	not provided
2	germline	unknown	46	not provided	discovery		not provided	0	not provided	not provided
3	germline	unknown	50	not provided	discovery		not provided	0	not provided	not provided
4	germline	unknown	62	not provided	discovery		not provided	0	not provided	not provided
5	germline	unknown	331	not provided	discovery		not provided	0	not provided	not provided
6	germline	unknown	118	not provided	discovery		not provided	0	not provided	not provided
7	germline	unknown	681	not provided	discovery		not provided	0.0007	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000916683.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: BLM c.3613G>A (p.Val1205Ile) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00078 in 278434 control chromosomes in the gnomAD database and publications, including 1 homozygote. The observed variant frequency within African control individuals in the gnomAD database is approximately 2.3-fold of the estimated maximal expected allele frequency for a pathogenic variant in BLM causing Bloom Syndrome phenotype (0.0035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The variant, c.3613G>A, has not been reported in the literature in individuals affected with Bloom Syndrome and was reported in healthy controls (Bodian_2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

#	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

From Genetic Services Laboratory, University of Chicago, SCV002071164.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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