chr8-11494752-G-T

Variant names:

• chr8-11494752-G-T
• rs13272061
• NM_001715.3:c.-2+161G>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+161G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,182 control chromosomes in the GnomAD database, including 13,048 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 0.37 (13048 hom., cov: 34)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 9 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 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.-2+161G>T		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.-91+161G>T		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.-2+161G>T		intron	N/A	ENSP00000259089.4
	BLK	ENST00000525389.1	TSL:1	n.423+161G>T		intron	N/A
	BLK	ENST00000645242.1		n.274+7585G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56433 AN: 152064 Hom.: 13052 Cov.: 34

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.371 AC: 56424 AN: 152182 Hom.: 13048 Cov.: 34 AF XY: 0.360 AC XY: 26818 AN XY: 74402

African (AFR) AF: 0.148 AC: 6127 AN: 41520

American (AMR) AF: 0.307 AC: 4690 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1918 AN: 3472

East Asian (EAS) AF: 0.00501 AC: 26 AN: 5190

South Asian (SAS) AF: 0.367 AC: 1768 AN: 4822

European-Finnish (FIN) AF: 0.390 AC: 4135 AN: 10590

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36479 AN: 67982

Other (OTH) AF: 0.394 AC: 833 AN: 2112

Alfa AF: 0.431 Hom.: 2350

Bravo AF: 0.349

Asia WGS AF: 0.168 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.47
PhyloP100		0.10
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs13272061; hg19: chr8-11352261;