8-11534141-A-G

Variant names:

• chr8-11534141-A-G
• rs2248932
• NM_001715.3:c.-1-9083A>G

Variant summary

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

The NM_001715.3(BLK):​c.-1-9083A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 152,108 control chromosomes in the GnomAD database, including 27,267 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 0.59 (27267 hom., cov: 33)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 40 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	NM_001715.3	MANE Select	c.-1-9083A>G		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.-90-11911A>G		intron	N/A	NP_001317394.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000259089.9	TSL:1 MANE Select	c.-1-9083A>G		intron	N/A	ENSP00000259089.4
	BLK	ENST00000645242.1		n.275-11911A>G		intron	N/A
	BLK	ENST00000696154.2		n.275-11911A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89742 AN: 151990 Hom.: 27252 Cov.: 33

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.590 AC: 89781 AN: 152108 Hom.: 27267 Cov.: 33 AF XY: 0.583 AC XY: 43340 AN XY: 74354

African (AFR) AF: 0.579 AC: 24036 AN: 41496

American (AMR) AF: 0.438 AC: 6701 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2502 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1393 AN: 5182

South Asian (SAS) AF: 0.525 AC: 2529 AN: 4814

European-Finnish (FIN) AF: 0.612 AC: 6471 AN: 10566

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44183 AN: 67984

Other (OTH) AF: 0.584 AC: 1233 AN: 2112

Alfa AF: 0.627 Hom.: 128365

Bravo AF: 0.571

Asia WGS AF: 0.385 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.78
PhyloP100		0.11
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: rs2248932; hg19: chr8-11391650;