rs2736345

Variant names:

• chr8-11494976-A-G
• rs2736345
• NM_001715.3:c.-2+385A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-11494976-A-G
• chr8-11494976-A-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.-2+385A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,066 control chromosomes in the GnomAD database, including 10,725 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 0.36 (10725 hom., cov: 33)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 36 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-2+385A>G		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.-2+385A>G		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000525389.1	n.423+385A>G		intron_variant	Intron 1 of 1	1
BLK	ENST00000645242.1	n.274+7809A>G		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+7809A>G		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54475 AN: 151948 Hom.: 10707 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.359 AC: 54533 AN: 152066 Hom.: 10725 Cov.: 33 AF XY: 0.366 AC XY: 27180 AN XY: 74334

African (AFR) AF: 0.362 AC: 15018 AN: 41450

American (AMR) AF: 0.518 AC: 7924 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 865 AN: 3468

East Asian (EAS) AF: 0.730 AC: 3768 AN: 5160

South Asian (SAS) AF: 0.434 AC: 2092 AN: 4816

European-Finnish (FIN) AF: 0.307 AC: 3250 AN: 10572

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.301 AC: 20452 AN: 67992

Other (OTH) AF: 0.357 AC: 756 AN: 2116

Alfa AF: 0.220 Hom.: 561

Bravo AF: 0.380

Asia WGS AF: 0.601 AC: 2088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.0
DANN	Benign	0.32
PhyloP100		-0.52
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: rs2736345; hg19: chr8-11352485;