chr8-11542970-C-A

Position:

• chr8-11542970-C-A

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.-1-254C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 152,270 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.028 (116 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.238

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-11542970-C-A is Benign according to our data. Variant chr8-11542970-C-A is described in ClinVar as [Benign]. Clinvar id is 1252213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.071 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.-1-254C>A		intron_variant		ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.-1-254C>A		intron_variant		1	NM_001715.3	P1
BLK	ENST00000645242.1	n.275-3082C>A		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.275-3082C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4205 AN: 152152 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.0732

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.00302

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0277 AC: 4211 AN: 152270 Hom.: 116 Cov.: 32 AF XY: 0.0262 AC XY: 1949 AN XY: 74456

Gnomad4 AFR AF: 0.0732

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00374

Gnomad4 FIN AF: 0.00302

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00616 Hom.: 3

Bravo AF: 0.0303

Asia WGS AF: 0.0110 AC: 39 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 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.81
DANN	Benign	0.68

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: rs74961098; hg19: chr8-11400479;