chr8-11488036-G-C

Variant names:

• chr8-11488036-G-C
• rs4840565
• ENST00000645242.1:n.274+869G>C

Variant summary

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

The ENST00000645242.1(BLK):​n.274+869G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,946 control chromosomes in the GnomAD database, including 9,245 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 0.33 (9245 hom., cov: 33)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 25 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 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+869G>C		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+869G>C		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50446 AN: 151828 Hom.: 9225 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.332 AC: 50503 AN: 151946 Hom.: 9245 Cov.: 33 AF XY: 0.339 AC XY: 25214 AN XY: 74270

African (AFR) AF: 0.323 AC: 13391 AN: 41412

American (AMR) AF: 0.472 AC: 7216 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3468

East Asian (EAS) AF: 0.734 AC: 3807 AN: 5190

South Asian (SAS) AF: 0.419 AC: 2017 AN: 4816

European-Finnish (FIN) AF: 0.298 AC: 3143 AN: 10544

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19146 AN: 67920

Other (OTH) AF: 0.330 AC: 697 AN: 2112

Alfa AF: 0.295 Hom.: 838

Bravo AF: 0.351

Asia WGS AF: 0.591 AC: 2052 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.25
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs4840565; hg19: chr8-11345545;