8-11564621-T-C

Position:

• chr8-11564621-T-C

Variant summary

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

The ENST00000602626.2(ENSG00000269954):​n.74A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 366,530 control chromosomes in the GnomAD database, including 28,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10753 hom., cov: 36)
  • Exomes 𝑓: 0.39 (17827 hom.)
• Consequence: ENSG00000269954 ENST00000602626.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.497

Genes affected

ENSG00000269954 (HGNC:):

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=-0.81).
• BP6: Variant 8-11564621-T-C is Benign according to our data. Variant chr8-11564621-T-C is described in ClinVar as [Benign]. Clinvar id is 1290380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLK	NM_001715.3	c.*513T>C		downstream_gene_variant		ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.*513T>C		downstream_gene_variant		1	NM_001715.3	ENSP00000259089.4

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52563 AN: 152152 Hom.: 10754 Cov.: 36

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.364

GnomAD3 exomes AF: 0.321 AC: 21341 AN: 66452 Hom.: 4297 AF XY: 0.325 AC XY: 11166 AN XY: 34344

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.532

Gnomad EAS exome AF: 0.0292

Gnomad SAS exome AF: 0.265

Gnomad FIN exome AF: 0.407

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.386 AC: 82690 AN: 214260 Hom.: 17827 Cov.: 0 AF XY: 0.372 AC XY: 43562 AN XY: 117110

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.505

Gnomad4 EAS exome AF: 0.0295

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.345 AC: 52567 AN: 152270 Hom.: 10753 Cov.: 36 AF XY: 0.336 AC XY: 24984 AN XY: 74450

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.0235

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.361

Alfa AF: 0.342 Hom.: 1686

Bravo AF: 0.329

Asia WGS AF: 0.154 AC: 539 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	clinical testing	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7843987; hg19: chr8-11422130;