8-11548666-G-A

Variant names:

• chr8-11548666-G-A
• rs17806523
• NM_001715.3:c.270-358G>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.270-358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,208 control chromosomes in the GnomAD database, including 1,531 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 0.12 (1531 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.270-358G>A		intron_variant	Intron 4 of 12	ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.270-358G>A		intron_variant	Intron 4 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000533828.1	n.468-358G>A		intron_variant	Intron 2 of 2	4
BLK	ENST00000645242.1	n.421-358G>A		intron_variant	Intron 3 of 11
BLK	ENST00000696154.2	n.421-358G>A		intron_variant	Intron 3 of 11

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18259 AN: 152090 Hom.: 1531 Cov.: 32

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0727

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.120 AC: 18269 AN: 152208 Hom.: 1531 Cov.: 32 AF XY: 0.115 AC XY: 8551 AN XY: 74422

African (AFR) AF: 0.0303 AC: 1259 AN: 41534

American (AMR) AF: 0.0838 AC: 1282 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3468

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0753 AC: 363 AN: 4822

European-Finnish (FIN) AF: 0.136 AC: 1442 AN: 10594

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12760 AN: 68006

Other (OTH) AF: 0.118 AC: 249 AN: 2112

Alfa AF: 0.151 Hom.: 2413

Bravo AF: 0.109

Asia WGS AF: 0.0390 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.088
DANN	Benign	0.57
PhyloP100		-1.5
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: rs17806523; hg19: chr8-11406175;