8-11542946-T-G

Variant names:

• chr8-11542946-T-G
• rs2245260
• NM_001715.3:c.-1-278T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001715.3(BLK):​c.-1-278T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 152,270 control chromosomes in the GnomAD database, including 75,420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 1.0 (75420 hom., cov: 31)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.74
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-11542946-T-G is Benign according to our data. Variant chr8-11542946-T-G is described in ClinVar as [Benign]. Clinvar id is 1271417.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-1-278T>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.-1-278T>G		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000645242.1	n.275-3106T>G		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.275-3106T>G		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.995 AC: 151434 AN: 152152 Hom.: 75362 Cov.: 31

Gnomad AFR AF: 0.985

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.995

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

GnomAD4 genome AF: 0.995 AC: 151551 AN: 152270 Hom.: 75420 Cov.: 31 AF XY: 0.996 AC XY: 74133 AN XY: 74462

African (AFR) AF: 0.985 AC: 40902 AN: 41540

American (AMR) AF: 0.997 AC: 15257 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3468 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5174

South Asian (SAS) AF: 1.00 AC: 4810 AN: 4810

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68012 AN: 68032

Other (OTH) AF: 0.996 AC: 2107 AN: 2116

Alfa AF: 0.996 Hom.: 4803

Bravo AF: 0.995

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 31, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.060
DANN	Benign	0.20
PhyloP100		-1.7
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: rs2245260; hg19: chr8-11400455;