rs1042695

Variant names:

• chr8-11564446-T-G
• rs1042695
• NM_001715.3:c.*338T>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001715.3(BLK):​c.*338T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00542 in 562,732 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0041 (5 hom., cov: 35)
  • Exomes 𝑓: 0.0059 (16 hom.)
• Consequence: BLK NM_001715.3 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 U:1 B:1
• Conservation: PhyloP100: -1.33
• Publications: 0 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: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

BLK-AS1 (HGNC:58190):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 8-11564446-T-G is Benign according to our data. Variant chr8-11564446-T-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 12320.
• BS2: High AC in GnomAd4 at 631 AD,Unknown gene.

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.*338T>G		3_prime_UTR	Exon 13 of 13	NP_001706.2
	BLK	NM_001330465.2		c.*338T>G		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.*338T>G		3_prime_UTR	Exon 13 of 13	ENSP00000259089.4	P51451
	BLK	ENST00000526097.1	TSL:1	n.1796T>G		non_coding_transcript_exon	Exon 3 of 3
	BLK	ENST00000855155.1		c.*338T>G		3_prime_UTR	Exon 13 of 13	ENSP00000525214.1

Frequencies

GnomAD3 genomes AF: 0.00414 AC: 630 AN: 152228 Hom.: 5 Cov.: 35

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.0279

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00545

Gnomad OTH AF: 0.00717

GnomAD2 exomes AF: 0.00636 AC: 820 AN: 128888 AF XY: 0.00636

Gnomad AFR exome AF: 0.00131

Gnomad AMR exome AF: 0.00411

Gnomad ASJ exome AF: 0.0264

Gnomad EAS exome AF: 0.000959

Gnomad FIN exome AF: 0.000375

Gnomad NFE exome AF: 0.00592

Gnomad OTH exome AF: 0.00501

GnomAD4 exome AF: 0.00589 AC: 2419 AN: 410386 Hom.: 16 Cov.: 0 AF XY: 0.00615 AC XY: 1392 AN XY: 226162

African (AFR) AF: 0.00185 AC: 23 AN: 12428

American (AMR) AF: 0.00404 AC: 122 AN: 30188

Ashkenazi Jewish (ASJ) AF: 0.0270 AC: 416 AN: 15392

East Asian (EAS) AF: 0.000517 AC: 10 AN: 19354

South Asian (SAS) AF: 0.00763 AC: 463 AN: 60664

European-Finnish (FIN) AF: 0.000452 AC: 9 AN: 19924

Middle Eastern (MID) AF: 0.0148 AC: 50 AN: 3382

European-Non Finnish (NFE) AF: 0.00521 AC: 1184 AN: 227282

Other (OTH) AF: 0.00652 AC: 142 AN: 21772

GnomAD4 genome AF: 0.00414 AC: 631 AN: 152346 Hom.: 5 Cov.: 35 AF XY: 0.00411 AC XY: 306 AN XY: 74500

African (AFR) AF: 0.00142 AC: 59 AN: 41586

American (AMR) AF: 0.00366 AC: 56 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 97 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00545 AC: 371 AN: 68024

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00750 Hom.: 0

Bravo AF: 0.00436

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
1	-	1	Maturity-onset diabetes of the young type 11 (2)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.7
DANN	Benign	0.27
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

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: rs1042695; hg19: chr8-11421955; COSMIC: COSV52056084; COSMIC: COSV52056084;