chr8-11495826-G-C

Variant names:

• chr8-11495826-G-C
• rs1478895
• NM_001715.3:c.-2+1235G>C

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+1235G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,170 control chromosomes in the GnomAD database, including 52,901 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 (52901 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.856 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	NM_001715.3	MANE Select	c.-2+1235G>C		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.-91+1235G>C		intron	N/A	NP_001317394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000259089.9	TSL:1 MANE Select	c.-2+1235G>C		intron	N/A	ENSP00000259089.4	P51451
	BLK	ENST00000525389.1	TSL:1	n.423+1235G>C		intron	N/A
	BLK	ENST00000645242.1		n.274+8659G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126522 AN: 152052 Hom.: 52851 Cov.: 32

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.832 AC: 126628 AN: 152170 Hom.: 52901 Cov.: 32 AF XY: 0.825 AC XY: 61372 AN XY: 74392

African (AFR) AF: 0.863 AC: 35820 AN: 41498

American (AMR) AF: 0.869 AC: 13278 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2885 AN: 3470

East Asian (EAS) AF: 0.735 AC: 3808 AN: 5184

South Asian (SAS) AF: 0.803 AC: 3878 AN: 4828

European-Finnish (FIN) AF: 0.699 AC: 7393 AN: 10580

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56955 AN: 68010

Other (OTH) AF: 0.825 AC: 1745 AN: 2114

Alfa AF: 0.846 Hom.: 6776

Bravo AF: 0.846

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.58
PhyloP100		-2.0
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: rs1478895; hg19: chr8-11353335;