rs62490888

chr8-11561257-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001715.3(BLK):c.1030-45G>A variant causes a intron 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 NM_001715.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.97

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-11561257-G-A is Benign according to our data. Variant chr8-11561257-G-A is described in ClinVar as [Benign]. Clinvar id is 1234817.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
BLK	NM_001715.3	c.1030-45G>A		intron_variant		ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.1030-45G>A		intron_variant		1	NM_001715.3	P1
	ENST00000602626.2	n.78-2271C>T		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.121 AC: 26909 AN: 223218 Hom.: 1781 AF XY: 0.123 AC XY: 14855 AN XY: 120436

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 SAS exome AF: 0.145

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

Gnomad4 AFR exome AF: 0.0406

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.0243

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.112

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

Gnomad4 AFR AF: 0.0459

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.0333

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.102

Alfa AF: 0.110 Hom.: 176

Bravo AF: 0.0961

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.017
Dann	Uncertain	0.99

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

Publications

LitVar

Other links and lift over

dbSNP: rs62490888; hg19: chr8-11418766;