rs2409782

Positions:

• chr8-11509583-T-C

Variant summary

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

The NM_001715.3(BLK):​c.-2+14992T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,992 control chromosomes in the GnomAD database, including 4,714 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 0.24 (4714 hom., cov: 31)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLK	NM_001715.3	c.-2+14992T>C		intron_variant		ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.-2+14992T>C		intron_variant		1	NM_001715.3	ENSP00000259089	P1
BLK	ENST00000525389.1	n.857T>C		non_coding_transcript_exon_variant	2/2	1
BLK	ENST00000645242.1	n.274+22416T>C		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+22416T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36636 AN: 151858 Hom.: 4713 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0182

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 2 AN XY: 12

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.241 AC: 36632 AN: 151976 Hom.: 4714 Cov.: 31 AF XY: 0.236 AC XY: 17521 AN XY: 74276

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.0180

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.213

Alfa AF: 0.245 Hom.: 747

Bravo AF: 0.231

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.61

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: rs2409782; hg19: chr8-11367092;