8-11561264-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000526097.1(BLK):n.932C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,599,138 control chromosomes in the GnomAD database, including 127,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13181 hom., cov: 33)

Exomes 𝑓: 0.38 ( 113873 hom. )

Consequence

BLK
ENST00000526097.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0220

Publications

11 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:

ENSG00000269954 (HGNC:58190):

ENSG00000269954 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.076).

BP6

Variant 8-11561264-C-T is Benign according to our data. Variant chr8-11561264-C-T is described in ClinVar as Benign. ClinVar VariationId is 1192426.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3 link	c.1030-38C>T		intron_variant	Intron 10 of 12	ENST00000259089.9	NP_001706.2	P51451Q05D26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9 link	c.1030-38C>T		intron_variant	Intron 10 of 12	1	NM_001715.3	ENSP00000259089.4		P51451

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60638

AN:

151914

Hom.:

13161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.563

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.924

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.352

Gnomad OTH

AF:

0.393

GnomAD2 exomes

AF:

0.444

AC:

101057

AN:

227774

AF XY:

0.439

show subpopulations

Gnomad AFR exome

AF:

0.358

Gnomad AMR exome

AF:

0.591

Gnomad ASJ exome

AF:

0.320

Gnomad EAS exome

AF:

0.923

Gnomad FIN exome

AF:

0.410

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.409

GnomAD4 exome

AF:

0.383

AC:

554266

AN:

1447106

Hom.:

113873

Cov.:

AF XY:

0.383

AC XY:

275386

AN XY:

718498

show subpopulations

African (AFR)

AF:

0.356

AC:

11815

AN:

33154

American (AMR)

AF:

0.583

AC:

24977

AN:

42834

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

8404

AN:

25912

East Asian (EAS)

AF:

0.919

AC:

35709

AN:

38836

South Asian (SAS)

AF:

0.455

AC:

38159

AN:

83882

European-Finnish (FIN)

AF:

0.408

AC:

21351

AN:

52348

Middle Eastern (MID)

AF:

0.345

AC:

1985

AN:

5756

European-Non Finnish (NFE)

AF:

0.351

AC:

387940

AN:

1104524

Other (OTH)

AF:

0.400

AC:

23926

AN:

59860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

16111

32221

48332

64442

80553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12754

25508

38262

51016

63770

<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:

0.399

AC:

60699

AN:

152032

Hom.:

13181

Cov.:

AF XY:

0.409

AC XY:

30408

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.361

AC:

14972

AN:

41488

American (AMR)

AF:

0.503

AC:

7689

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

1136

AN:

3468

East Asian (EAS)

AF:

0.924

AC:

4761

AN:

5154

South Asian (SAS)

AF:

0.468

AC:

2249

AN:

4802

European-Finnish (FIN)

AF:

0.430

AC:

4545

AN:

10580

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.352

AC:

23898

AN:

67932

Other (OTH)

AF:

0.401

AC:

848

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1729

3458

5186

6915

8644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.356

Hom.:

1871

Bravo

AF:

0.410

Asia WGS

AF:

0.670

AC:

2328

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Maturity-onset diabetes of the young type 11

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Systemic lupus erythematosus

Benign:1

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

BLK gene is associated with Systemic lupus erythematosus, sjogren's syndrome and other systemic inflammatory conditions. However no sufficient evidence is found to ascertain the role of this particular variant rs4841561, yet. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.3

(source)

DANN

Uncertain

1.0

PhyloP100

0.022

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over