ENST00000525389.1:n.802G>C

Variant names:

• chr8-11509528-G-C
• rs4629826
• ENST00000525389.1:n.802G>C

Variant summary

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

The ENST00000525389.1(BLK):​n.802G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,240 control chromosomes in the GnomAD database, including 777 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 0.092 (776 hom., cov: 32)
  • Exomes 𝑓: 0.077 (1 hom.)
• Consequence: BLK ENST00000525389.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525389.1. 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+14937G>C		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.-91+14937G>C		intron	N/A	NP_001317394.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000525389.1	TSL:1	n.802G>C		non_coding_transcript_exon	Exon 2 of 2
	BLK	ENST00000259089.9	TSL:1 MANE Select	c.-2+14937G>C		intron	N/A	ENSP00000259089.4
	BLK	ENST00000645242.1		n.274+22361G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13986 AN: 152096 Hom.: 775 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0714

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.0787

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.0673

GnomAD4 exome AF: 0.0769 AC: 2 AN: 26 Hom.: 1 Cov.: 0 AF XY: 0.100 AC XY: 2 AN XY: 20

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0833 AC: 2 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0918 AC: 13980 AN: 152214 Hom.: 776 Cov.: 32 AF XY: 0.0913 AC XY: 6798 AN XY: 74422

African (AFR) AF: 0.112 AC: 4643 AN: 41536

American (AMR) AF: 0.0562 AC: 860 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 248 AN: 3472

East Asian (EAS) AF: 0.0164 AC: 85 AN: 5168

South Asian (SAS) AF: 0.0782 AC: 377 AN: 4824

European-Finnish (FIN) AF: 0.113 AC: 1199 AN: 10598

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0923 AC: 6276 AN: 67990

Other (OTH) AF: 0.0662 AC: 140 AN: 2116

Alfa AF: 0.0559 Hom.: 78

Bravo AF: 0.0867

Asia WGS AF: 0.0540 AC: 188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.36
PhyloP100		0.25
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: rs4629826; hg19: chr8-11367037;