dbSNP rs17273206: BLM:c.2308-50G>A (chr15-90769083-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000057.4(BLM):c.2308-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,363,766 control chromosomes in the GnomAD database, including 19,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2084 hom., cov: 32)

Exomes 𝑓: 0.16 ( 16960 hom. )

Consequence

BLM
NM_000057.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.357

Variant links:

Genes affected

BLM (HGNC:1058): (BLM RecQ like helicase) The Bloom syndrome is an autosomal recessive disorder characterized by growth deficiency, microcephaly and immunodeficiency among others. It is caused by homozygous or compound heterozygous mutation in the gene encoding DNA helicase RecQ protein on chromosome 15q26. This Bloom-associated helicase unwinds a variety of DNA substrates including Holliday junction, and is involved in several pathways contributing to the maintenance of genome stability. Identification of pathogenic Bloom variants is required for heterozygote testing in at-risk families. [provided by RefSeq, May 2020]

BLM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 15-90769083-G-A is Benign according to our data. Variant chr15-90769083-G-A is described in ClinVar as [Benign]. Clinvar id is 254778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLM	NM_000057.4 link	c.2308-50G>A		intron_variant	Intron 10 of 21	ENST00000355112.8	NP_000048.1	P54132

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLM	ENST00000355112.8 link	c.2308-50G>A		intron_variant	Intron 10 of 21	1	NM_000057.4	ENSP00000347232.3		P54132

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24751

AN:

152058

Hom.:

2086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.0769

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.0884

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.152

GnomAD3 exomes

AF:

0.153

AC:

38439

AN:

251152

Hom.:

3193

AF XY:

0.149

AC XY:

20293

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.0789

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.162

AC:

195945

AN:

1211590

Hom.:

16960

Cov.:

AF XY:

0.159

AC XY:

97925

AN XY:

615054

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.0811

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.159

GnomAD4 genome

AF:

0.163

AC:

24764

AN:

152176

Hom.:

2084

Cov.:

AF XY:

0.159

AC XY:

11799

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.167

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.0881

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.153

Alfa

AF:

0.173

Hom.:

575

Bravo

AF:

0.163

Asia WGS

AF:

0.159

AC:

555

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bloom syndrome

Benign:3

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 06, 2018

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.27

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over