chr19-50833976-T-C

Variant names:

• chr19-50833976-T-C
• rs2659055
• ENST00000695965.1:c.-481A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000695965.1(KLK15):​c.-481A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,958 control chromosomes in the GnomAD database, including 15,284 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (15284 hom., cov: 30)
• Consequence: KLK15 ENST00000695965.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 6 publications found

Genes affected

KLK15 (HGNC:20453): (kallikrein related peptidase 15) Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. In prostate cancer, this gene has increased expression, which indicates its possible use as a diagnostic or prognostic marker for prostate cancer. The gene contains multiple polyadenylation sites and alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ENSG00000267968 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000695965.1. 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
	LOC105372441	NR_131203.1		n.213+2683T>C		intron	N/A
	LOC105372441	NR_131205.1		n.230+2683T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	ENST00000695965.1		c.-481A>G		5_prime_UTR	Exon 1 of 5	ENSP00000512291.1	Q9H2R5-4
	KLK15	ENST00000906215.1		c.-32+1601A>G		intron	N/A	ENSP00000576274.1
	KLK15	ENST00000326856.8	TSL:5	c.-31-2453A>G		intron	N/A	ENSP00000314783.4	Q9H2R5-5

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65510 AN: 151840 Hom.: 15276 Cov.: 30

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.452

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.431 AC: 65541 AN: 151958 Hom.: 15284 Cov.: 30 AF XY: 0.439 AC XY: 32583 AN XY: 74256

African (AFR) AF: 0.227 AC: 9420 AN: 41454

American (AMR) AF: 0.508 AC: 7750 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1624 AN: 3468

East Asian (EAS) AF: 0.563 AC: 2904 AN: 5156

South Asian (SAS) AF: 0.468 AC: 2250 AN: 4810

European-Finnish (FIN) AF: 0.598 AC: 6315 AN: 10554

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33648 AN: 67944

Other (OTH) AF: 0.456 AC: 965 AN: 2114

Alfa AF: 0.454 Hom.: 5891

Bravo AF: 0.413

Asia WGS AF: 0.513 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.50
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2659055; hg19: chr19-51337232;