Genetic Variant NM_001715.3:c.-2+14937G>C (chr8-11509528-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001715.3(BLK):c.-2+14937G>C variant causes a intron 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
NM_001715.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.254

Publications

2 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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: 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+14937G>C		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.-91+14937G>C		intron	N/A	NP_001317394.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BLK	ENST00000259089.9	TSL:1 MANE Select	c.-2+14937G>C	intron	N/A	ENSP00000259089.4	P51451
BLK	ENST00000525389.1	TSL:1	n.802G>C	non_coding_transcript_exon	Exon 2 of 2
BLK	ENST00000645242.1		n.274+22361G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0920

AC:

13986

AN:

152096

Hom.:

775

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.100

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0833

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0918

AC:

13980

AN:

152214

Hom.:

776

Cov.:

AF XY:

0.0913

AC XY:

6798

AN XY:

74422

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0923

AC:

6276

AN:

67990

Other (OTH)

AF:

0.0662

AC:

140

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

634

1269

1903

2538

3172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0559

Hom.:

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

(source)

DANN

Benign

0.36

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over