rs1478890

chr8-11498093-C-Gchr8-11498093-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.-2+3502C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,070 control chromosomes in the GnomAD database, including 12,920 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 0.37 (12920 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.-2+3502C>G		intron_variant		ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.-2+3502C>G		intron_variant		1	NM_001715.3	P1
BLK	ENST00000525389.1	n.423+3502C>G		intron_variant, non_coding_transcript_variant		1
BLK	ENST00000645242.1	n.274+10926C>G		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+10926C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56829 AN: 151952 Hom.: 12924 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.374 AC: 56822 AN: 152070 Hom.: 12920 Cov.: 32 AF XY: 0.363 AC XY: 27012 AN XY: 74314

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.396

Alfa AF: 0.341 Hom.: 1070

Bravo AF: 0.353

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.26
Dann	Benign	0.34

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: rs1478890; hg19: chr8-11355602;