rs1042701

Positions:

• chr8-11564536-G-A

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.*428G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 477,818 control chromosomes in the GnomAD database, including 38,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (10731 hom., cov: 36)
  • Exomes 𝑓: 0.39 (28084 hom.)
• Consequence: BLK NM_001715.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0950

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 8-11564536-G-A is Benign according to our data. Variant chr8-11564536-G-A is described in ClinVar as [Benign]. Clinvar id is 361506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11564536-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLK	NM_001715.3	c.*428G>A		3_prime_UTR_variant	13/13	ENST00000259089.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLK	ENST00000259089.9	c.*428G>A		3_prime_UTR_variant	13/13	1	NM_001715.3	P1
	ENST00000602626.2	n.77+82C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52492 AN: 152148 Hom.: 10732 Cov.: 36

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.364

GnomAD3 exomes AF: 0.345 AC: 44280 AN: 128162 Hom.: 9153 AF XY: 0.350 AC XY: 24470 AN XY: 69884

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.523

Gnomad EAS exome AF: 0.0276

Gnomad SAS exome AF: 0.275

Gnomad FIN exome AF: 0.407

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.395 AC: 128455 AN: 325552 Hom.: 28084 Cov.: 0 AF XY: 0.389 AC XY: 71152 AN XY: 183118

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.0307

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.405

GnomAD4 genome AF: 0.345 AC: 52496 AN: 152266 Hom.: 10731 Cov.: 36 AF XY: 0.335 AC XY: 24950 AN XY: 74456

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.0235

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.360

Alfa AF: 0.441 Hom.: 2707

Bravo AF: 0.328

Asia WGS AF: 0.154 AC: 539 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

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

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 rs1042701, yet. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.84

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: rs1042701; hg19: chr8-11422045;