rs2255227

Positions:

• chr8-11553029-C-T

Variant summary

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

The NM_001715.3(BLK):​c.473-1714C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 162,476 control chromosomes in the GnomAD database, including 73,446 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 0.95 (68529 hom., cov: 37)
  • Exomes 𝑓: 0.98 (4917 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.473-1714C>T		intron_variant		ENST00000259089.9
LOC105379241	XR_948956.3	n.1729G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.473-1714C>T		intron_variant		1	NM_001715.3	P1
	ENST00000602626.2	n.1248G>A		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes AF: 0.946 AC: 144037 AN: 152204 Hom.: 68486 Cov.: 37

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.944

GnomAD4 exome AF: 0.984 AC: 9991 AN: 10154 Hom.: 4917 Cov.: 0 AF XY: 0.985 AC XY: 5190 AN XY: 5268

Gnomad4 AFR exome AF: 0.831

Gnomad4 AMR exome AF: 0.972

Gnomad4 ASJ exome AF: 0.951

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.998

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.991

Gnomad4 OTH exome AF: 0.973

GnomAD4 genome AF: 0.946 AC: 144138 AN: 152322 Hom.: 68529 Cov.: 37 AF XY: 0.948 AC XY: 70596 AN XY: 74488

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.947

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 0.998

Gnomad4 NFE AF: 0.987

Gnomad4 OTH AF: 0.945

Alfa AF: 0.966 Hom.: 8843

Bravo AF: 0.941

Asia WGS AF: 0.984 AC: 3421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.71
DANN	Benign	0.50

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: rs2255227; hg19: chr8-11410538;