NM_001715.3:c.1313-28C>T

Variant names:

• chr8-11563875-C-T
• rs10097015
• NM_001715.3:c.1313-28C>T

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.1313-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,594,148 control chromosomes in the GnomAD database, including 133,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14801 hom., cov: 34)
  • Exomes 𝑓: 0.39 (118985 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.858
• Publications: 10 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

BLK-AS1 (HGNC:58190):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-11563875-C-T is Benign according to our data. Variant chr8-11563875-C-T is described in ClinVar as Benign. ClinVar VariationId is 1192495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 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.1313-28C>T		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.1100-28C>T		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.1313-28C>T		intron	N/A	ENSP00000259089.4	P51451
	BLK	ENST00000526097.1	TSL:1	n.1253-28C>T		intron	N/A
	BLK	ENST00000855155.1		c.1313-28C>T		intron	N/A	ENSP00000525214.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64707 AN: 152038 Hom.: 14772 Cov.: 34

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.418

GnomAD2 exomes AF: 0.468 AC: 96928 AN: 206998 AF XY: 0.460

Gnomad AFR exome AF: 0.444

Gnomad AMR exome AF: 0.606

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.921

Gnomad FIN exome AF: 0.403

Gnomad NFE exome AF: 0.359

Gnomad OTH exome AF: 0.418

GnomAD4 exome AF: 0.393 AC: 566106 AN: 1441992 Hom.: 118985 Cov.: 35 AF XY: 0.394 AC XY: 282020 AN XY: 716564

African (AFR) AF: 0.432 AC: 14260 AN: 32978

American (AMR) AF: 0.597 AC: 25914 AN: 43424

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 9074 AN: 25834

East Asian (EAS) AF: 0.918 AC: 35583 AN: 38756

South Asian (SAS) AF: 0.490 AC: 41281 AN: 84326

European-Finnish (FIN) AF: 0.404 AC: 19106 AN: 47334

Middle Eastern (MID) AF: 0.367 AC: 1997 AN: 5448

European-Non Finnish (NFE) AF: 0.357 AC: 394269 AN: 1104300

Other (OTH) AF: 0.413 AC: 24622 AN: 59592

GnomAD4 genome AF: 0.426 AC: 64785 AN: 152156 Hom.: 14801 Cov.: 34 AF XY: 0.436 AC XY: 32395 AN XY: 74366

African (AFR) AF: 0.434 AC: 18032 AN: 41512

American (AMR) AF: 0.521 AC: 7960 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1234 AN: 3470

East Asian (EAS) AF: 0.924 AC: 4762 AN: 5156

South Asian (SAS) AF: 0.502 AC: 2420 AN: 4822

European-Finnish (FIN) AF: 0.429 AC: 4551 AN: 10598

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24325 AN: 67992

Other (OTH) AF: 0.425 AC: 897 AN: 2110

Alfa AF: 0.379 Hom.: 2101

Bravo AF: 0.440

Asia WGS AF: 0.694 AC: 2411 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Maturity-onset diabetes of the young type 11 (1)
-	-	1	Systemic lupus erythematosus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.90
PhyloP100		0.86
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: rs10097015; hg19: chr8-11421384;