8-11543340-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001715.3(BLK):c.116C>T(p.Pro39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,613,148 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 8 hom. )

Consequence

BLK
NM_001715.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 3.47

Publications

16 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: Unknown, AD Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021823794).

BP6

Variant 8-11543340-C-T is Benign according to our data. Variant chr8-11543340-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 300 AD,Unknown gene.

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.116C>T	p.Pro39Leu	missense	Exon 2 of 13	NP_001706.2
	BLK	NM_001330465.2		c.-90-2712C>T		intron	N/A	NP_001317394.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BLK	ENST00000259089.9	TSL:1 MANE Select	c.116C>T	p.Pro39Leu	missense	Exon 2 of 13	ENSP00000259089.4
BLK	ENST00000855155.1		c.116C>T	p.Pro39Leu	missense	Exon 2 of 13	ENSP00000525214.1
BLK	ENST00000855156.1		c.116C>T	p.Pro39Leu	missense	Exon 1 of 12	ENSP00000525215.1

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

300

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00320

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00222

AC:

554

AN:

249222

AF XY:

0.00239

show subpopulations

Gnomad AFR exome

AF:

0.000687

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.00339

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00281

AC:

4103

AN:

1460846

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

2016

AN XY:

726812

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33480

American (AMR)

AF:

0.00333

AC:

149

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000574

AC:

AN:

26136

East Asian (EAS)

AF:

0.000176

AC:

AN:

39700

South Asian (SAS)

AF:

0.000638

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00103

AC:

AN:

52406

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00328

AC:

3652

AN:

1111996

Other (OTH)

AF:

0.00229

AC:

138

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

255

510

764

1019

1274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<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:

0.00197

AC:

300

AN:

152302

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

129

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000626

AC:

AN:

41562

American (AMR)

AF:

0.00209

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00320

AC:

218

AN:

68030

Other (OTH)

AF:

0.00284

AC:

AN:

2112

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

Genome Het

Genome Hom

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

Alfa

AF:

0.00131

Hom.:

Bravo

AF:

0.00208

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00227

AC:

276

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00439

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (2)

Maturity-onset diabetes of the young type 11 (1)

Systemic lupus erythematosus (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Benign

-0.10

Eigen_PC

Benign

0.024

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.55

PhyloP100

3.5

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.0

REVEL

Benign

0.29

Sift

Benign

0.032

Sift4G

Uncertain

0.023

Polyphen

0.55

Vest4

0.62

MVP

0.88

MPC

0.074

ClinPred

0.030

GERP RS

5.5

Varity_R

0.092

gMVP

0.36

Mutation Taster

=92/8

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over