8-11554314-G-A

Variant names:

• chr8-11554314-G-A
• rs17744726
• NM_001715.3:c.473-429G>A

Variant summary

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

The NM_001715.3(BLK):​c.473-429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 253,032 control chromosomes in the GnomAD database, including 8,219 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 0.23 (4743 hom., cov: 32)
  • Exomes 𝑓: 0.24 (3476 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462
• Publications: 13 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

BLK-AS1 (HGNC:58190):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 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.473-429G>A		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.260-429G>A		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.473-429G>A		intron	N/A	ENSP00000259089.4
	BLK	ENST00000855155.1		c.473-429G>A		intron	N/A	ENSP00000525214.1
	BLK	ENST00000855156.1		c.473-429G>A		intron	N/A	ENSP00000525215.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35103 AN: 151912 Hom.: 4745 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.239 AC: 24111 AN: 101002 Hom.: 3476 AF XY: 0.234 AC XY: 12376 AN XY: 52902

African (AFR) AF: 0.124 AC: 471 AN: 3796

American (AMR) AF: 0.168 AC: 933 AN: 5552

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 828 AN: 2284

East Asian (EAS) AF: 0.00379 AC: 22 AN: 5812

South Asian (SAS) AF: 0.161 AC: 2276 AN: 14142

European-Finnish (FIN) AF: 0.210 AC: 628 AN: 2988

Middle Eastern (MID) AF: 0.242 AC: 90 AN: 372

European-Non Finnish (NFE) AF: 0.288 AC: 17515 AN: 60716

Other (OTH) AF: 0.252 AC: 1348 AN: 5340

GnomAD4 genome AF: 0.231 AC: 35095 AN: 152030 Hom.: 4743 Cov.: 32 AF XY: 0.224 AC XY: 16618 AN XY: 74294

African (AFR) AF: 0.131 AC: 5423 AN: 41480

American (AMR) AF: 0.210 AC: 3204 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3470

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5178

South Asian (SAS) AF: 0.184 AC: 882 AN: 4794

European-Finnish (FIN) AF: 0.223 AC: 2358 AN: 10560

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21028 AN: 67946

Other (OTH) AF: 0.254 AC: 535 AN: 2110

Alfa AF: 0.290 Hom.: 11140

Bravo AF: 0.222

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.75
PhyloP100		0.46
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: rs17744726; hg19: chr8-11411823;