8-11494152-C-A

Position:

• chr8-11494152-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000645242.1(BLK):​n.274+6985C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 152,320 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BLK ENST00000645242.1 intron, non_coding_transcript
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.860

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 8-11494152-C-A is Benign according to our data. Variant chr8-11494152-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 361461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 611 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000645242.1	n.274+6985C>A		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+6985C>A		intron_variant, non_coding_transcript_variant
BLK	ENST00000525389.1			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00401 AC: 611 AN: 152202 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00475

Gnomad OTH AF: 0.00766

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 30

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00401 AC: 611 AN: 152320 Hom.: 2 Cov.: 33 AF XY: 0.00431 AC XY: 321 AN XY: 74490

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.00475

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00165 Hom.: 0

Bravo AF: 0.00350

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Maturity onset diabetes mellitus in young Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

BLK: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.0
DANN	Benign	0.78

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: rs142686759; hg19: chr8-11351661;