8-11543171-G-A

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.-1-53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,610,296 control chromosomes in the GnomAD database, including 176,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13810 hom., cov: 31)
  • Exomes 𝑓: 0.46 (163156 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.369

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=-0.82).
• BP6: Variant 8-11543171-G-A is Benign according to our data. Variant chr8-11543171-G-A is described in ClinVar as [Benign]. Clinvar id is 1192423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.-1-53G>A		intron_variant		ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.-1-53G>A		intron_variant		1	NM_001715.3	P1
BLK	ENST00000645242.1	n.275-2881G>A		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.275-2881G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62361 AN: 151882 Hom.: 13808 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.460 AC: 671426 AN: 1458296 Hom.: 163156 AF XY: 0.458 AC XY: 332016 AN XY: 725480

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.00212

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.502

Gnomad4 OTH exome AF: 0.450

GnomAD4 genome AF: 0.410 AC: 62367 AN: 152000 Hom.: 13810 Cov.: 31 AF XY: 0.397 AC XY: 29509 AN XY: 74302

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.00521

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.422

Alfa AF: 0.475 Hom.: 2210

Bravo AF: 0.400

Asia WGS AF: 0.164 AC: 574 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Maturity-onset diabetes of the young type 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Systemic lupus erythematosus Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

-

BLK gene is associated with Systemic lupus erythematosus, sjogren's syndrome and other systemic inflammatory conditions. However no sufficient evidence is found to ascertain the role of this particular variant rs2245250, yet. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.9
Dann	Benign	0.75

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

Other links and lift over

dbSNP: rs2245250; hg19: chr8-11400680; COSMIC: COSV52057589; COSMIC: COSV52057589;