8-11494403-C-T

Position:

• chr8-11494403-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.-190C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,170 control chromosomes in the GnomAD database, including 8,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8896 hom., cov: 32)
  • Exomes 𝑓: 0.28 (2 hom.)
• Consequence: BLK NM_001715.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38

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=-0.74).
• BP6: Variant 8-11494403-C-T is Benign according to our data. Variant chr8-11494403-C-T is described in ClinVar as [Benign]. Clinvar id is 361468.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.-190C>T		5_prime_UTR_variant	1/13	ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.-190C>T		5_prime_UTR_variant	1/13	1	NM_001715.3	P1
BLK	ENST00000525389.1	n.235C>T		non_coding_transcript_exon_variant	1/2	1
BLK	ENST00000645242.1	n.274+7236C>T		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.274+7236C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48852 AN: 151988 Hom.: 8879 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.321

GnomAD4 exome AF: 0.281 AC: 18 AN: 64 Hom.: 2 Cov.: 0 AF XY: 0.283 AC XY: 13 AN XY: 46

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.322 AC: 48904 AN: 152106 Hom.: 8896 Cov.: 32 AF XY: 0.329 AC XY: 24465 AN XY: 74342

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.329

Alfa AF: 0.311 Hom.: 5086

Bravo AF: 0.339

Asia WGS AF: 0.584 AC: 2030 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Maturity-onset diabetes of the young type 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.79

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: rs922483; hg19: chr8-11351912;