rs17744726

Positions:

• chr8-11554314-G-A

Variant summary

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

The NM_001715.3(BLK):​c.473-429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 253,032 control chromosomes in the GnomAD database, including 8,219 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 0.23 (4743 hom., cov: 32)
  • Exomes 𝑓: 0.24 (3476 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462

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]

(HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.473-429G>A		intron_variant		ENST00000259089.9
LOC105379241	XR_948956.3	n.1118-111C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.473-429G>A		intron_variant		1	NM_001715.3	P1
	ENST00000602626.2	n.623-111C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35103 AN: 151912 Hom.: 4745 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.239 AC: 24111 AN: 101002 Hom.: 3476 AF XY: 0.234 AC XY: 12376 AN XY: 52902

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.00379

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.231 AC: 35095 AN: 152030 Hom.: 4743 Cov.: 32 AF XY: 0.224 AC XY: 16618 AN XY: 74294

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.254

Alfa AF: 0.296 Hom.: 9125

Bravo AF: 0.222

Asia WGS AF: 0.107 AC: 374 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	4.1
DANN	Benign	0.75

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: rs17744726; hg19: chr8-11411823;