rs4841557

chr8-11558063-A-G

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.1029+25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,611,546 control chromosomes in the GnomAD database, including 283,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26267 hom., cov: 33)
  • Exomes 𝑓: 0.58 (256928 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0200

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]

LOC105379241 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-11558063-A-G is Benign according to our data. Variant chr8-11558063-A-G is described in ClinVar as [Benign]. Clinvar id is 1182428.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.1029+25A>G		intron_variant		ENST00000259089.9
LOC105379241	XR_948956.3	n.203T>C		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.1029+25A>G		intron_variant		1	NM_001715.3	P1
	ENST00000602626.2	n.242-85T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87393 AN: 151944 Hom.: 26250 Cov.: 33

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.560

GnomAD3 exomes AF: 0.521 AC: 130680 AN: 250634 Hom.: 37470 AF XY: 0.524 AC XY: 70936 AN XY: 135452

Gnomad AFR exome AF: 0.639

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.660

Gnomad EAS exome AF: 0.0604

Gnomad SAS exome AF: 0.454

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.619

Gnomad OTH exome AF: 0.565

GnomAD4 exome AF: 0.583 AC: 851439 AN: 1459484 Hom.: 256928 Cov.: 32 AF XY: 0.581 AC XY: 422173 AN XY: 726120

Gnomad4 AFR exome AF: 0.644

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.660

Gnomad4 EAS exome AF: 0.0572

Gnomad4 SAS exome AF: 0.457

Gnomad4 FIN exome AF: 0.570

Gnomad4 NFE exome AF: 0.618

Gnomad4 OTH exome AF: 0.568

GnomAD4 genome AF: 0.575 AC: 87451 AN: 152062 Hom.: 26267 Cov.: 33 AF XY: 0.564 AC XY: 41900 AN XY: 74320

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.0585

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.553

Alfa AF: 0.618 Hom.: 5481

Bravo AF: 0.565

Asia WGS AF: 0.279 AC: 974 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	-0.92
Cadd	Benign	3.8
Dann	Benign	0.66

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: rs4841557; hg19: chr8-11415572; COSMIC: COSV52049361; COSMIC: COSV52049361;