rs3816668

Variant names:

• chr8-11549084-T-C
• rs3816668
• NM_001715.3:c.330T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-11549084-T-C
• chr8-11549084-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001715.3(BLK):​c.330T>C​(p.Ser110Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,609,686 control chromosomes in the GnomAD database, including 196,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18684 hom., cov: 32)
  • Exomes 𝑓: 0.49 (177742 hom.)
• Consequence: BLK NM_001715.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.386
• Publications: 26 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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 8-11549084-T-C is Benign according to our data. Variant chr8-11549084-T-C is described in ClinVar as Benign. ClinVar VariationId is 128527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.386 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 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.330T>C	p.Ser110Ser	synonymous	Exon 5 of 13	NP_001706.2
	BLK	NM_001330465.2		c.117T>C	p.Ser39Ser	synonymous	Exon 4 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.330T>C	p.Ser110Ser	synonymous	Exon 5 of 13	ENSP00000259089.4	P51451
	BLK	ENST00000855155.1		c.330T>C	p.Ser110Ser	synonymous	Exon 5 of 13	ENSP00000525214.1
	BLK	ENST00000855156.1		c.330T>C	p.Ser110Ser	synonymous	Exon 4 of 12	ENSP00000525215.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73752 AN: 151890 Hom.: 18672 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.493

GnomAD2 exomes AF: 0.443 AC: 107849 AN: 243242 AF XY: 0.451

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.331

Gnomad ASJ exome AF: 0.625

Gnomad EAS exome AF: 0.0708

Gnomad FIN exome AF: 0.419

Gnomad NFE exome AF: 0.510

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.486 AC: 708594 AN: 1457678 Hom.: 177742 Cov.: 56 AF XY: 0.488 AC XY: 353435 AN XY: 724500

African (AFR) AF: 0.525 AC: 17572 AN: 33440

American (AMR) AF: 0.338 AC: 14912 AN: 44180

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 16239 AN: 26062

East Asian (EAS) AF: 0.0666 AC: 2643 AN: 39668

South Asian (SAS) AF: 0.466 AC: 39660 AN: 85038

European-Finnish (FIN) AF: 0.422 AC: 22470 AN: 53184

Middle Eastern (MID) AF: 0.527 AC: 3037 AN: 5764

European-Non Finnish (NFE) AF: 0.507 AC: 562969 AN: 1110058

Other (OTH) AF: 0.483 AC: 29092 AN: 60284

GnomAD4 genome AF: 0.486 AC: 73806 AN: 152008 Hom.: 18684 Cov.: 32 AF XY: 0.478 AC XY: 35494 AN XY: 74296

African (AFR) AF: 0.524 AC: 21737 AN: 41450

American (AMR) AF: 0.420 AC: 6413 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2147 AN: 3468

East Asian (EAS) AF: 0.0738 AC: 381 AN: 5166

South Asian (SAS) AF: 0.458 AC: 2205 AN: 4816

European-Finnish (FIN) AF: 0.414 AC: 4373 AN: 10556

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35046 AN: 67958

Other (OTH) AF: 0.488 AC: 1030 AN: 2112

Alfa AF: 0.512 Hom.: 41899

Bravo AF: 0.481

Asia WGS AF: 0.284 AC: 992 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Maturity-onset diabetes of the young type 11 (2)
-	-	2	not specified (2)
-	-	1	Systemic lupus erythematosus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		-0.39
Mutation Taster		=98/2	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: rs3816668; hg19: chr8-11406593; COSMIC: COSV52052315; COSMIC: COSV52052315;