rs2409782

Variant names:

• chr8-11509583-T-C
• rs2409782
• NM_001715.3:c.-2+14992T>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+14992T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,992 control chromosomes in the GnomAD database, including 4,714 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 0.24 (4714 hom., cov: 31)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 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+14992T>C		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.-91+14992T>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+14992T>C		intron	N/A	ENSP00000259089.4
	BLK	ENST00000525389.1	TSL:1	n.857T>C		non_coding_transcript_exon	Exon 2 of 2
	BLK	ENST00000645242.1		n.274+22416T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36636 AN: 151858 Hom.: 4713 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0182

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 2 AN XY: 12

African (AFR) AC: 0 AN: 0

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: 0.214 AC: 3 AN: 14

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.241 AC: 36632 AN: 151976 Hom.: 4714 Cov.: 31 AF XY: 0.236 AC XY: 17521 AN XY: 74276

African (AFR) AF: 0.274 AC: 11350 AN: 41450

American (AMR) AF: 0.152 AC: 2318 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3472

East Asian (EAS) AF: 0.0180 AC: 93 AN: 5164

South Asian (SAS) AF: 0.216 AC: 1041 AN: 4816

European-Finnish (FIN) AF: 0.254 AC: 2679 AN: 10542

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17683 AN: 67938

Other (OTH) AF: 0.213 AC: 448 AN: 2108

Alfa AF: 0.250 Hom.: 7232

Bravo AF: 0.231

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.61
PhyloP100		0.72
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: rs2409782; hg19: chr8-11367092;