NM_001715.3:c.175+157C>G

Variant names:

• chr8-11546260-C-G
• rs2244931
• NM_001715.3:c.175+157C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001715.3(BLK):​c.175+157C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,994 control chromosomes in the GnomAD database, including 17,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.46 (17846 hom., cov: 32)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.609
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-11546260-C-G is Benign according to our data. Variant chr8-11546260-C-G is described in ClinVar as Benign. ClinVar VariationId is 1292676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	NM_001715.3	MANE Select	c.175+157C>G		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.-39+157C>G		intron	N/A	NP_001317394.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000259089.9	TSL:1 MANE Select	c.175+157C>G		intron	N/A	ENSP00000259089.4
	BLK	ENST00000855155.1		c.175+157C>G		intron	N/A	ENSP00000525214.1
	BLK	ENST00000855156.1		c.175+157C>G		intron	N/A	ENSP00000525215.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69544 AN: 151876 Hom.: 17838 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.458 AC: 69572 AN: 151994 Hom.: 17846 Cov.: 32 AF XY: 0.472 AC XY: 35091 AN XY: 74290

African (AFR) AF: 0.242 AC: 10049 AN: 41452

American (AMR) AF: 0.580 AC: 8868 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1344 AN: 3460

East Asian (EAS) AF: 0.826 AC: 4262 AN: 5162

South Asian (SAS) AF: 0.656 AC: 3152 AN: 4804

European-Finnish (FIN) AF: 0.633 AC: 6688 AN: 10570

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33637 AN: 67952

Other (OTH) AF: 0.447 AC: 945 AN: 2112

Alfa AF: 0.240 Hom.: 518

Bravo AF: 0.448

Asia WGS AF: 0.691 AC: 2402 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.61
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: rs2244931; hg19: chr8-11403769; COSMIC: COSV107264993; COSMIC: COSV107264993;