8-11543119-C-G

Variant summary

Our verdict is Benign. Variant got -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:3
• Conservation: PhyloP100: -0.165

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BLK	NM_001715.3	c.-1-105C>G		intron_variant		ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.-1-105C>G		intron_variant		1	NM_001715.3	P1
BLK	ENST00000645242.1	n.275-2933C>G		intron_variant, non_coding_transcript_variant
BLK	ENST00000696154.2	n.275-2933C>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.751

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.594

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.541

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

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.562

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Maturity-onset diabetes of the young type 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Systemic lupus erythematosus Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

-

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.5
Dann	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs12386974; hg19: chr8-11400628;