8-11543141-G-A

Position:

• chr8-11543141-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001715.3(BLK):​c.-1-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,605,214 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (115 hom., cov: 33)
  • Exomes 𝑓: 0.014 (237 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.103

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-11543141-G-A is Benign according to our data. Variant chr8-11543141-G-A is described in ClinVar as [Benign]. Clinvar id is 1293437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLK	NM_001715.3	c.-1-83G>A		intron_variant		ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.-1-83G>A		intron_variant		1	NM_001715.3	ENSP00000259089	P1
BLK	ENST00000645242.1	n.275-2911G>A		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.275-2911G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4219 AN: 152102 Hom.: 114 Cov.: 33

Gnomad AFR AF: 0.0734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.0135 AC: 19661 AN: 1452994 Hom.: 237 AF XY: 0.0131 AC XY: 9473 AN XY: 722884

Gnomad4 AFR exome AF: 0.0757

Gnomad4 AMR exome AF: 0.00765

Gnomad4 ASJ exome AF: 0.00622

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.00581

Gnomad4 FIN exome AF: 0.00377

Gnomad4 NFE exome AF: 0.0136

Gnomad4 OTH exome AF: 0.0130

GnomAD4 genome AF: 0.0278 AC: 4225 AN: 152220 Hom.: 115 Cov.: 33 AF XY: 0.0262 AC XY: 1953 AN XY: 74438

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00375

Gnomad4 FIN AF: 0.00330

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00590 Hom.: 2

Bravo AF: 0.0304

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.85
CADD	Benign	0.34
DANN	Benign	0.55

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: rs80167929; hg19: chr8-11400650;