8-11564284-C-T

Variant names:

• chr8-11564284-C-T
• rs1042689
• NM_001715.3:c.*176C>T

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.*176C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 779,138 control chromosomes in the GnomAD database, including 76,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15566 hom., cov: 35)
  • Exomes 𝑓: 0.42 (61159 hom.)
• Consequence: BLK NM_001715.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0230

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]

ENSG00000269954 (HGNC:58190):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 8-11564284-C-T is Benign according to our data. Variant chr8-11564284-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 361500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3	c.*176C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000259089.9	NP_001706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000259089.9	c.*176C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_001715.3	ENSP00000259089.4

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66462 AN: 152096 Hom.: 15539 Cov.: 35

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.426

GnomAD3 exomes AF: 0.483 AC: 61432 AN: 127312 Hom.: 16605 AF XY: 0.476 AC XY: 32990 AN XY: 69340

Gnomad AFR exome AF: 0.482

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.923

Gnomad SAS exome AF: 0.495

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.429

GnomAD4 exome AF: 0.416 AC: 261107 AN: 626924 Hom.: 61159 Cov.: 8 AF XY: 0.417 AC XY: 138457 AN XY: 331880

Gnomad4 AFR exome AF: 0.472

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.919

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.437 AC: 66542 AN: 152214 Hom.: 15566 Cov.: 35 AF XY: 0.447 AC XY: 33268 AN XY: 74418

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.434

Alfa AF: 0.400 Hom.: 4697

Bravo AF: 0.452

Asia WGS AF: 0.698 AC: 2424 AN: 3478

ClinVar

Significance: Benign/Likely 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

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. -

Systemic lupus erythematosus Benign:1

-

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance: Likely 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 rs1042689, yet. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.2
DANN	Benign	0.80

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: rs1042689; hg19: chr8-11421793;