8-11543141-G-A

Variant names:

• chr8-11543141-G-A
• rs80167929
• NM_001715.3:c.-1-83G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001715.3(BLK):​c.-1-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,605,214 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (115 hom., cov: 33)
  • Exomes 𝑓: 0.014 (237 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.103
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-11543141-G-A is Benign according to our data. Variant chr8-11543141-G-A is described in ClinVar as [Benign]. Clinvar id is 1293437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-1-83G>A		intron_variant	Intron 1 of 12	ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.-1-83G>A		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000645242.1	n.275-2911G>A		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.275-2911G>A		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4219 AN: 152102 Hom.: 114 Cov.: 33

Gnomad AFR AF: 0.0734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.0135 AC: 19661 AN: 1452994 Hom.: 237 AF XY: 0.0131 AC XY: 9473 AN XY: 722884

African (AFR) AF: 0.0757 AC: 2524 AN: 33364

American (AMR) AF: 0.00765 AC: 341 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.00622 AC: 162 AN: 26040

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39608

South Asian (SAS) AF: 0.00581 AC: 497 AN: 85482

European-Finnish (FIN) AF: 0.00377 AC: 185 AN: 49028

Middle Eastern (MID) AF: 0.0159 AC: 88 AN: 5540

European-Non Finnish (NFE) AF: 0.0136 AC: 15072 AN: 1109260

Other (OTH) AF: 0.0130 AC: 784 AN: 60124

GnomAD4 genome AF: 0.0278 AC: 4225 AN: 152220 Hom.: 115 Cov.: 33 AF XY: 0.0262 AC XY: 1953 AN XY: 74438

African (AFR) AF: 0.0734 AC: 3048 AN: 41528

American (AMR) AF: 0.0136 AC: 208 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.00375 AC: 18 AN: 4806

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10610

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0124 AC: 842 AN: 68004

Other (OTH) AF: 0.0156 AC: 33 AN: 2110

Alfa AF: 0.00590 Hom.: 2

Bravo AF: 0.0304

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.34
DANN	Benign	0.55
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs80167929; hg19: chr8-11400650;