8-11494547-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001715.3(BLK):c.-46A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,266 control chromosomes in the GnomAD database, including 51,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51503 hom., cov: 33)

Exomes 𝑓: 0.81 ( 15 hom. )

Consequence

BLK
NM_001715.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00

Publications

14 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 8-11494547-A-G is Benign according to our data. Variant chr8-11494547-A-G is described in ClinVar as [Benign]. Clinvar id is 361471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3 link	c.-46A>G		5_prime_UTR_variant	Exon 1 of 13	ENST00000259089.9	NP_001706.2	P51451Q05D26

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BLK	ENST00000525389.1 link	n.379A>G	non_coding_transcript_exon_variant	Exon 1 of 2	1
BLK	ENST00000259089.9 link	c.-46A>G	5_prime_UTR_variant	Exon 1 of 13	1	NM_001715.3	ENSP00000259089.4	P51451
BLK	ENST00000645242.1 link	n.274+7380A>G	intron_variant	Intron 1 of 11
BLK	ENST00000696154.2 link	n.274+7380A>G	intron_variant	Intron 1 of 11				A0A8Q3SIE3

Frequencies

GnomAD3 genomes

AF:

0.821

AC:

124904

AN:

152108

Hom.:

51462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.827

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.863

Gnomad ASJ

AF:

0.830

Gnomad EAS

AF:

0.736

Gnomad SAS

AF:

0.796

Gnomad FIN

AF:

0.698

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.837

Gnomad OTH

AF:

0.814

GnomAD4 exome

AF:

0.810

AC:

AN:

Hom.:

Cov.:

AF XY:

0.861

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:

0.824

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.821

AC:

125002

AN:

152224

Hom.:

51503

Cov.:

AF XY:

0.815

AC XY:

60632

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.827

AC:

34331

AN:

41534

American (AMR)

AF:

0.863

AC:

13209

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.830

AC:

2882

AN:

3472

East Asian (EAS)

AF:

0.736

AC:

3816

AN:

5184

South Asian (SAS)

AF:

0.796

AC:

3842

AN:

4826

European-Finnish (FIN)

AF:

0.698

AC:

7386

AN:

10582

Middle Eastern (MID)

AF:

0.844

AC:

248

AN:

294

European-Non Finnish (NFE)

AF:

0.837

AC:

56952

AN:

68014

Other (OTH)

AF:

0.817

AC:

1721

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1133

2266

3398

4531

5664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.842

Hom.:

24585

Bravo

AF:

0.834

Asia WGS

AF:

0.795

AC:

2765

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Maturity-onset diabetes of the young type 11

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.2

(source)

DANN

Benign

0.46

PhyloP100

0.0

PromoterAI

0.076

Neutral

(source)

Mutation Taster

=300/0

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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8-11494547-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over