8-11535371-T-C

Variant names:

• chr8-11535371-T-C
• rs9329246
• NM_001715.3:c.-1-7853T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001715.3(BLK):​c.-1-7853T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,420 control chromosomes in the GnomAD database, including 11,306 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11306 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 8 publications found

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]

BLK Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• maturity-onset diabetes of the young type 11

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-1-7853T>C		intron_variant	Intron 1 of 12	ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.-1-7853T>C		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000645242.1	n.275-10681T>C		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.275-10681T>C		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56031 AN: 151298 Hom.: 11280 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.356

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.370 AC: 56092 AN: 151420 Hom.: 11306 Cov.: 32 AF XY: 0.379 AC XY: 28070 AN XY: 73974

African (AFR) AF: 0.309 AC: 12768 AN: 41270

American (AMR) AF: 0.540 AC: 8236 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3460

East Asian (EAS) AF: 0.735 AC: 3778 AN: 5142

South Asian (SAS) AF: 0.465 AC: 2219 AN: 4776

European-Finnish (FIN) AF: 0.388 AC: 4058 AN: 10454

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.338 AC: 22909 AN: 67770

Other (OTH) AF: 0.382 AC: 802 AN: 2098

Alfa AF: 0.344 Hom.: 1854

Bravo AF: 0.385

Asia WGS AF: 0.590 AC: 2002 AN: 3402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.62
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9329246; hg19: chr8-11392880;