rs1042701

Variant names:

• chr8-11564536-G-A
• rs1042701
• NM_001715.3:c.*428G>A

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.*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:4
• Conservation: PhyloP100: -0.0950
• Publications: 14 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: Unknown, AD Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

BLK-AS1 (HGNC:58190):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 361506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001715.3. 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.*428G>A		3_prime_UTR	Exon 13 of 13	NP_001706.2
	BLK	NM_001330465.2		c.*428G>A		3_prime_UTR	Exon 12 of 12	NP_001317394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000259089.9	TSL:1 MANE Select	c.*428G>A		3_prime_UTR	Exon 13 of 13	ENSP00000259089.4	P51451
	BLK	ENST00000526097.1	TSL:1	n.1886G>A		non_coding_transcript_exon	Exon 3 of 3
	BLK	ENST00000855155.1		c.*428G>A		3_prime_UTR	Exon 13 of 13	ENSP00000525214.1

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

GnomAD2 exomes AF: 0.345 AC: 44280 AN: 128162 AF XY: 0.350

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 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

African (AFR) AF: 0.176 AC: 1683 AN: 9552

American (AMR) AF: 0.247 AC: 6849 AN: 27726

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 6083 AN: 11804

East Asian (EAS) AF: 0.0307 AC: 342 AN: 11130

South Asian (SAS) AF: 0.275 AC: 16387 AN: 59574

European-Finnish (FIN) AF: 0.407 AC: 5534 AN: 13604

Middle Eastern (MID) AF: 0.462 AC: 1361 AN: 2944

European-Non Finnish (NFE) AF: 0.483 AC: 83814 AN: 173428

Other (OTH) AF: 0.405 AC: 6402 AN: 15790

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

African (AFR) AF: 0.169 AC: 7034 AN: 41564

American (AMR) AF: 0.308 AC: 4711 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3472

East Asian (EAS) AF: 0.0235 AC: 122 AN: 5186

South Asian (SAS) AF: 0.267 AC: 1288 AN: 4830

European-Finnish (FIN) AF: 0.372 AC: 3943 AN: 10602

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32415 AN: 67986

Other (OTH) AF: 0.360 AC: 762 AN: 2114

Alfa AF: 0.434 Hom.: 2716

Bravo AF: 0.328

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Maturity-onset diabetes of the young type 11 (1)
-	-	1	Systemic lupus erythematosus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.84
PhyloP100		-0.095
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: rs1042701; hg19: chr8-11422045;