8-11539309-C-T

Variant names:

• chr8-11539309-C-T
• rs7014565
• NM_001715.3:c.-1-3915C>T

Variant summary

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

The NM_001715.3(BLK):​c.-1-3915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,128 control chromosomes in the GnomAD database, including 1,618 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 0.13 (1618 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001715.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	NM_001715.3	MANE Select	c.-1-3915C>T		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.-90-6743C>T		intron	N/A	NP_001317394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000259089.9	TSL:1 MANE Select	c.-1-3915C>T		intron	N/A	ENSP00000259089.4	P51451
	BLK	ENST00000855155.1		c.-264C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000525214.1
	BLK	ENST00000855155.1		c.-264C>T		5_prime_UTR	Exon 1 of 13	ENSP00000525214.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20378 AN: 152010 Hom.: 1616 Cov.: 32

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.0931

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.134 AC: 20381 AN: 152128 Hom.: 1618 Cov.: 32 AF XY: 0.142 AC XY: 10560 AN XY: 74346

African (AFR) AF: 0.0859 AC: 3564 AN: 41512

American (AMR) AF: 0.0932 AC: 1424 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3472

East Asian (EAS) AF: 0.242 AC: 1251 AN: 5180

South Asian (SAS) AF: 0.230 AC: 1109 AN: 4816

European-Finnish (FIN) AF: 0.251 AC: 2648 AN: 10544

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9382 AN: 68004

Other (OTH) AF: 0.135 AC: 284 AN: 2108

Alfa AF: 0.127 Hom.: 2592

Bravo AF: 0.119

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		0.052
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: rs7014565; hg19: chr8-11396818;