8-11546260-C-G

Position:

• chr8-11546260-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001715.3(BLK):​c.175+157C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,994 control chromosomes in the GnomAD database, including 17,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.46 (17846 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.609

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-11546260-C-G is Benign according to our data. Variant chr8-11546260-C-G is described in ClinVar as [Benign]. Clinvar id is 1292676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLK	NM_001715.3	c.175+157C>G		intron_variant		ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.175+157C>G		intron_variant		1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000533828.1	n.373+157C>G		intron_variant		4
BLK	ENST00000645242.1	n.326+157C>G		intron_variant
BLK	ENST00000696154.2	n.326+157C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69544 AN: 151876 Hom.: 17838 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.444

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.458 AC: 69572 AN: 151994 Hom.: 17846 Cov.: 32 AF XY: 0.472 AC XY: 35091 AN XY: 74290

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.447

Alfa AF: 0.240 Hom.: 518

Bravo AF: 0.448

Asia WGS AF: 0.691 AC: 2402 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.89
CADD	Benign	1.2
DANN	Benign	0.47

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: rs2244931; hg19: chr8-11403769;