chr8-11543119-C-G

Variant names:

• chr8-11543119-C-G
• rs12386974
• NM_001715.3:c.-1-105C>G

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.-1-105C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,577,420 control chromosomes in the GnomAD database, including 236,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25363 hom., cov: 32)
  • Exomes 𝑓: 0.53 (211141 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.165
• Publications: 6 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=-0.82).
• BP6: Variant 8-11543119-C-G is Benign according to our data. Variant chr8-11543119-C-G is described in ClinVar as [Benign]. Clinvar id is 1192422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.-1-105C>G		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.-1-105C>G		intron_variant	Intron 1 of 12	1	NM_001715.3	ENSP00000259089.4
BLK	ENST00000645242.1	n.275-2933C>G		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.275-2933C>G		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86054 AN: 151970 Hom.: 25329 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.534 AC: 760882 AN: 1425332 Hom.: 211141 AF XY: 0.537 AC XY: 380549 AN XY: 708966

African (AFR) AF: 0.575 AC: 18894 AN: 32854

American (AMR) AF: 0.751 AC: 32422 AN: 43184

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 10518 AN: 25712

East Asian (EAS) AF: 0.998 AC: 39210 AN: 39294

South Asian (SAS) AF: 0.696 AC: 58648 AN: 84214

European-Finnish (FIN) AF: 0.594 AC: 26661 AN: 44888

Middle Eastern (MID) AF: 0.507 AC: 2482 AN: 4896

European-Non Finnish (NFE) AF: 0.495 AC: 540080 AN: 1091154

Other (OTH) AF: 0.541 AC: 31967 AN: 59136

GnomAD4 genome AF: 0.566 AC: 86139 AN: 152088 Hom.: 25363 Cov.: 32 AF XY: 0.580 AC XY: 43125 AN XY: 74362

African (AFR) AF: 0.575 AC: 23833 AN: 41470

American (AMR) AF: 0.664 AC: 10160 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1395 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5147 AN: 5174

South Asian (SAS) AF: 0.706 AC: 3397 AN: 4814

European-Finnish (FIN) AF: 0.631 AC: 6674 AN: 10574

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33605 AN: 67972

Other (OTH) AF: 0.562 AC: 1186 AN: 2112

Alfa AF: 0.372 Hom.: 950

Bravo AF: 0.574

Asia WGS AF: 0.828 AC: 2875 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 rs12386974, yet. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-0.17
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: rs12386974; hg19: chr8-11400628;