rs58373594

chr8-11533118-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001715.3(BLK):c.-1-10106A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,130 control chromosomes in the GnomAD database, including 1,691 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1691 hom., cov: 33)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.-1-10106A>T		intron_variant		ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.-1-10106A>T		intron_variant		1	NM_001715.3	P1
BLK	ENST00000645242.1	n.275-12934A>T		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.275-12934A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21178 AN: 152012 Hom.: 1690 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.0997

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.139 AC: 21190 AN: 152130 Hom.: 1691 Cov.: 33 AF XY: 0.147 AC XY: 10899 AN XY: 74364

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0997

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.141

Alfa AF: 0.128 Hom.: 175

Bravo AF: 0.126

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.9
Dann	Benign	0.72

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: rs58373594; hg19: chr8-11390627;