8-11490151-C-T

Variant names:

• chr8-11490151-C-T
• rs1478900
• ENST00000645242.1:n.274+2984C>T

Variant summary

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

The ENST00000645242.1(BLK):​n.274+2984C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,190 control chromosomes in the GnomAD database, including 52,271 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 0.83 (52271 hom., cov: 33)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000645242.1	n.274+2984C>T		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+2984C>T		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125785 AN: 152072 Hom.: 52215 Cov.: 33

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.827 AC: 125900 AN: 152190 Hom.: 52271 Cov.: 33 AF XY: 0.820 AC XY: 60982 AN XY: 74402

African (AFR) AF: 0.860 AC: 35708 AN: 41506

American (AMR) AF: 0.845 AC: 12937 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2896 AN: 3470

East Asian (EAS) AF: 0.726 AC: 3752 AN: 5166

South Asian (SAS) AF: 0.788 AC: 3810 AN: 4832

European-Finnish (FIN) AF: 0.691 AC: 7307 AN: 10576

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56891 AN: 68012

Other (OTH) AF: 0.821 AC: 1735 AN: 2114

Alfa AF: 0.841 Hom.: 8705

Bravo AF: 0.839

Asia WGS AF: 0.789 AC: 2742 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.6
DANN	Benign	0.66
PhyloP100		-0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1478900; hg19: chr8-11347660;