ENST00000526097.1:n.925G>A

Variant names:

• chr8-11561257-G-A
• rs62490888
• ENST00000526097.1:n.925G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000526097.1(BLK):​n.925G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,596,468 control chromosomes in the GnomAD database, including 13,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1032 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12323 hom.)
• Consequence: BLK ENST00000526097.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.97
• Publications: 9 publications found

Genes affected

BLK (HGNC:1057): (BLK proto-oncogene, Src family tyrosine kinase) This gene encodes a nonreceptor tyrosine-kinase of the src family of proto-oncogenes that are typically involved in cell proliferation and differentiation. The protein has a role in B-cell receptor signaling and B-cell development. The protein also stimulates insulin synthesis and secretion in response to glucose and enhances the expression of several pancreatic beta-cell transcription factors. [provided by RefSeq, Aug 2010]

BLK Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• maturity-onset diabetes of the young type 11

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000269954 (HGNC:58190):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.024).
• BP6: Variant 8-11561257-G-A is Benign according to our data. Variant chr8-11561257-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.1030-45G>A		intron_variant	Intron 10 of 12	ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.1030-45G>A		intron_variant	Intron 10 of 12	1	NM_001715.3	ENSP00000259089.4

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16030 AN: 152144 Hom.: 1034 Cov.: 33

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0334

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.121 AC: 26909 AN: 223218 AF XY: 0.123

Gnomad AFR exome AF: 0.0433

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.0325

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.127 AC: 183160 AN: 1444206 Hom.: 12323 Cov.: 31 AF XY: 0.128 AC XY: 91484 AN XY: 716790

African (AFR) AF: 0.0406 AC: 1343 AN: 33070

American (AMR) AF: 0.104 AC: 4419 AN: 42324

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2676 AN: 25870

East Asian (EAS) AF: 0.0243 AC: 940 AN: 38666

South Asian (SAS) AF: 0.144 AC: 12052 AN: 83480

European-Finnish (FIN) AF: 0.168 AC: 8756 AN: 52168

Middle Eastern (MID) AF: 0.110 AC: 630 AN: 5752

European-Non Finnish (NFE) AF: 0.132 AC: 145680 AN: 1103120

Other (OTH) AF: 0.112 AC: 6664 AN: 59756

GnomAD4 genome AF: 0.105 AC: 16024 AN: 152262 Hom.: 1032 Cov.: 33 AF XY: 0.108 AC XY: 8025 AN XY: 74454

African (AFR) AF: 0.0459 AC: 1908 AN: 41564

American (AMR) AF: 0.0970 AC: 1485 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3470

East Asian (EAS) AF: 0.0333 AC: 172 AN: 5162

South Asian (SAS) AF: 0.140 AC: 676 AN: 4824

European-Finnish (FIN) AF: 0.180 AC: 1916 AN: 10618

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9207 AN: 68002

Other (OTH) AF: 0.102 AC: 215 AN: 2110

Alfa AF: 0.123 Hom.: 1706

Bravo AF: 0.0961

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 09, 2018

GeneDx

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	0.017
DANN	Uncertain	0.99
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs62490888; hg19: chr8-11418766;