rs7843987

Variant names:

• chr8-11564621-T-C
• rs7843987
• ENST00000602626.2:n.74A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-11564621-T-C
• chr8-11564621-T-A

Variant summary

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

The ENST00000602626.2(BLK-AS1):​n.74A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 366,530 control chromosomes in the GnomAD database, including 28,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10753 hom., cov: 36)
  • Exomes 𝑓: 0.39 (17827 hom.)
• Consequence: BLK-AS1 ENST00000602626.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.497
• Publications: 9 publications found

Genes affected

BLK-AS1 (HGNC:58190):

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=-0.81).
• BP6: Variant 8-11564621-T-C is Benign according to our data. Variant chr8-11564621-T-C is described in ClinVar as Benign. ClinVar VariationId is 1290380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000602626.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	NM_001715.3	MANE Select	c.*513T>C		downstream_gene	N/A	NP_001706.2
	BLK	NM_001330465.2		c.*513T>C		downstream_gene	N/A	NP_001317394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK-AS1	ENST00000602626.2	TSL:6	n.74A>G		non_coding_transcript_exon	Exon 1 of 9
	BLK	ENST00000259089.9	TSL:1 MANE Select	c.*513T>C		downstream_gene	N/A	ENSP00000259089.4	P51451
	BLK	ENST00000526097.1	TSL:1	n.*22T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52563 AN: 152152 Hom.: 10754 Cov.: 36

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.364

GnomAD2 exomes AF: 0.321 AC: 21341 AN: 66452 AF XY: 0.325

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.532

Gnomad EAS exome AF: 0.0292

Gnomad FIN exome AF: 0.407

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.386 AC: 82690 AN: 214260 Hom.: 17827 Cov.: 0 AF XY: 0.372 AC XY: 43562 AN XY: 117110

African (AFR) AF: 0.166 AC: 943 AN: 5690

American (AMR) AF: 0.247 AC: 4110 AN: 16670

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 2698 AN: 5344

East Asian (EAS) AF: 0.0295 AC: 228 AN: 7726

South Asian (SAS) AF: 0.273 AC: 12519 AN: 45852

European-Finnish (FIN) AF: 0.405 AC: 3717 AN: 9180

Middle Eastern (MID) AF: 0.463 AC: 1076 AN: 2324

European-Non Finnish (NFE) AF: 0.479 AC: 53252 AN: 111248

Other (OTH) AF: 0.406 AC: 4147 AN: 10226

GnomAD4 genome AF: 0.345 AC: 52567 AN: 152270 Hom.: 10753 Cov.: 36 AF XY: 0.336 AC XY: 24984 AN XY: 74450

African (AFR) AF: 0.170 AC: 7060 AN: 41560

American (AMR) AF: 0.308 AC: 4712 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1783 AN: 3470

East Asian (EAS) AF: 0.0235 AC: 122 AN: 5190

South Asian (SAS) AF: 0.267 AC: 1291 AN: 4828

European-Finnish (FIN) AF: 0.372 AC: 3948 AN: 10604

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32458 AN: 67994

Other (OTH) AF: 0.361 AC: 763 AN: 2116

Alfa AF: 0.336 Hom.: 1695

Bravo AF: 0.329

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.41
PhyloP100		-0.50
Mutation Taster		=96/4	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7843987; hg19: chr8-11422130;