rs998683

Variant names:

• chr8-11495491-G-A
• rs998683
• NM_001715.3:c.-2+900G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-11495491-G-A
• chr8-11495491-G-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.-2+900G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,162 control chromosomes in the GnomAD database, including 6,658 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 0.26 (6658 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-2+900G>A		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+900G>A		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000525389.1	n.423+900G>A		intron_variant	Intron 1 of 1	1
BLK	ENST00000645242.1	n.274+8324G>A		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+8324G>A		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40081 AN: 152044 Hom.: 6637 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.264 AC: 40117 AN: 152162 Hom.: 6658 Cov.: 32 AF XY: 0.271 AC XY: 20159 AN XY: 74382

African (AFR) AF: 0.140 AC: 5799 AN: 41524

American (AMR) AF: 0.453 AC: 6923 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3470

East Asian (EAS) AF: 0.705 AC: 3646 AN: 5172

South Asian (SAS) AF: 0.351 AC: 1691 AN: 4822

European-Finnish (FIN) AF: 0.273 AC: 2891 AN: 10576

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17818 AN: 67986

Other (OTH) AF: 0.273 AC: 578 AN: 2114

Alfa AF: 0.277 Hom.: 1167

Bravo AF: 0.278

Asia WGS AF: 0.527 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-0.15
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: rs998683; hg19: chr8-11353000;