19-50834136-C-T

Variant names:

• chr19-50834136-C-T
• rs2163861
• ENST00000695965.1:c.-641G>A

Variant summary

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

The ENST00000695965.1(KLK15):​c.-641G>A 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 151,798 control chromosomes in the GnomAD database, including 15,279 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 (15279 hom., cov: 30)
• Consequence: KLK15 ENST00000695965.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC105372441	NR_131203.1		n.213+2843C>T		intron	N/A
	LOC105372441	NR_131205.1		n.230+2843C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	ENST00000695965.1		c.-641G>A		5_prime_UTR	Exon 1 of 5	ENSP00000512291.1
	KLK15	ENST00000326856.8	TSL:5	c.-31-2613G>A		intron	N/A	ENSP00000314783.4
	ENSG00000267968	ENST00000598079.1	TSL:3	n.213+2843C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65467 AN: 151680 Hom.: 15271 Cov.: 30

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.600

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: 65498 AN: 151798 Hom.: 15279 Cov.: 30 AF XY: 0.439 AC XY: 32554 AN XY: 74146

African (AFR) AF: 0.227 AC: 9411 AN: 41400

American (AMR) AF: 0.508 AC: 7746 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1626 AN: 3464

East Asian (EAS) AF: 0.564 AC: 2906 AN: 5154

South Asian (SAS) AF: 0.469 AC: 2249 AN: 4796

European-Finnish (FIN) AF: 0.600 AC: 6306 AN: 10512

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

European-Non Finnish (NFE) AF: 0.495 AC: 33623 AN: 67912

Other (OTH) AF: 0.456 AC: 963 AN: 2110

Alfa AF: 0.474 Hom.: 26832

Bravo AF: 0.413

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		-0.49
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: rs2163861; hg19: chr19-51337392;