Genetic Variant BLK:c.-2+14942C>T (chr8-11509533-C-T) – 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+14942C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,230 control chromosomes in the GnomAD database, including 1,101 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 0.10 ( 1101 hom., cov: 32)

Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

BLK
NM_001715.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.105

Publications

6 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 (NFE) allele frequency at 95% confidence interval = 0.157 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+14942C>T		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.-91+14942C>T		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+14942C>T	intron	N/A	ENSP00000259089.4	P51451
BLK	ENST00000525389.1	TSL:1	n.807C>T	non_coding_transcript_exon	Exon 2 of 2
BLK	ENST00000645242.1		n.274+22366C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15898

AN:

152100

Hom.:

1103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0294

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0666

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.167

AC:

AN:

Hom.:

Cov.:

AF XY:

0.100

AC XY:

AN XY:

show subpopulations

African (AFR)

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:

0.167

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.104

AC:

15891

AN:

152218

Hom.:

1101

Cov.:

AF XY:

0.101

AC XY:

7535

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0293

AC:

1217

AN:

41562

American (AMR)

AF:

0.0664

AC:

1016

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3466

East Asian (EAS)

AF:

0.00116

AC:

AN:

5164

South Asian (SAS)

AF:

0.128

AC:

618

AN:

4826

European-Finnish (FIN)

AF:

0.136

AC:

1441

AN:

10596

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10869

AN:

67990

Other (OTH)

AF:

0.0996

AC:

210

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

701

1402

2102

2803

3504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.134

Hom.:

272

Bravo

AF:

0.0941

Asia WGS

AF:

0.0530

AC:

186

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

3.8

(source)

DANN

Benign

0.71

PhyloP100

-0.10

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over