rs1042689

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-11564284-C-T
• chr8-11564284-C-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.*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
• Publications: 11 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 -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 Benign/Likely_benign. ClinVar VariationId 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.

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.*176C>T		3_prime_UTR	Exon 13 of 13	NP_001706.2
	BLK	NM_001330465.2		c.*176C>T		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.*176C>T		3_prime_UTR	Exon 13 of 13	ENSP00000259089.4	P51451
	BLK	ENST00000526097.1	TSL:1	n.1634C>T		non_coding_transcript_exon	Exon 3 of 3
	BLK	ENST00000855155.1		c.*176C>T		3_prime_UTR	Exon 13 of 13	ENSP00000525214.1

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

GnomAD2 exomes AF: 0.483 AC: 61432 AN: 127312 AF XY: 0.476

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 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

African (AFR) AF: 0.472 AC: 8014 AN: 16970

American (AMR) AF: 0.590 AC: 20266 AN: 34378

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 7098 AN: 20170

East Asian (EAS) AF: 0.919 AC: 29555 AN: 32152

South Asian (SAS) AF: 0.492 AC: 30931 AN: 62920

European-Finnish (FIN) AF: 0.407 AC: 13414 AN: 32934

Middle Eastern (MID) AF: 0.360 AC: 1511 AN: 4202

European-Non Finnish (NFE) AF: 0.350 AC: 136453 AN: 390308

Other (OTH) AF: 0.422 AC: 13865 AN: 32890

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

African (AFR) AF: 0.473 AC: 19652 AN: 41528

American (AMR) AF: 0.522 AC: 7989 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1233 AN: 3472

East Asian (EAS) AF: 0.923 AC: 4780 AN: 5176

South Asian (SAS) AF: 0.505 AC: 2438 AN: 4826

European-Finnish (FIN) AF: 0.430 AC: 4558 AN: 10608

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24372 AN: 67996

Other (OTH) AF: 0.434 AC: 915 AN: 2110

Alfa AF: 0.393 Hom.: 7121

Bravo AF: 0.452

Asia WGS AF: 0.698 AC: 2424 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.78
CADD	Benign	8.2
DANN	Benign	0.80
PhyloP100		0.023
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: rs1042689; hg19: chr8-11421793;