rs4841558

chr8-11558088-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001715.3(BLK):c.1029+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,576,564 control chromosomes in the GnomAD database, including 275,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (25763 hom., cov: 33)
  • Exomes 𝑓: 0.58 (250147 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.51

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]

LOC105379241 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-11558088-C-T is Benign according to our data. Variant chr8-11558088-C-T is described in ClinVar as [Benign]. Clinvar id is 1253200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.1029+50C>T		intron_variant		ENST00000259089.9
LOC105379241	XR_948956.3	n.178G>A		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.1029+50C>T		intron_variant		1	NM_001715.3	P1
	ENST00000602626.2	n.242-110G>A		intron_variant, non_coding_transcript_variant
BLK	ENST00000645242.1	n.1180+50C>T		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.1137+34C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86623 AN: 151952 Hom.: 25759 Cov.: 33

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.554

GnomAD3 exomes AF: 0.520 AC: 129183 AN: 248324 Hom.: 36816 AF XY: 0.523 AC XY: 70178 AN XY: 134224

Gnomad AFR exome AF: 0.624

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.659

Gnomad EAS exome AF: 0.0602

Gnomad SAS exome AF: 0.454

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.619

Gnomad OTH exome AF: 0.565

GnomAD4 exome AF: 0.583 AC: 830270 AN: 1424494 Hom.: 250147 Cov.: 23 AF XY: 0.581 AC XY: 412992 AN XY: 710888

Gnomad4 AFR exome AF: 0.626

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.659

Gnomad4 EAS exome AF: 0.0570

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.570

Gnomad4 NFE exome AF: 0.618

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.570 AC: 86661 AN: 152070 Hom.: 25763 Cov.: 33 AF XY: 0.558 AC XY: 41510 AN XY: 74326

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.0583

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.547

Alfa AF: 0.615 Hom.: 5432

Bravo AF: 0.560

Asia WGS AF: 0.275 AC: 962 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.31
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4841558; hg19: chr8-11415597; COSMIC: COSV52051446; COSMIC: COSV52051446;