19-50835917-G-A

Variant names:

• chr19-50835917-G-A
• rs2739442
• ENST00000326856.8:c.-32+1198C>T

Variant summary

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

The ENST00000326856.8(KLK15):​c.-32+1198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 152,078 control chromosomes in the GnomAD database, including 18,183 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 0.48 (18183 hom., cov: 33)
• Consequence: KLK15 ENST00000326856.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000326856.8. 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+4624G>A		intron	N/A
	LOC105372441	NR_131205.1		n.230+4624G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	ENST00000326856.8	TSL:5	c.-32+1198C>T		intron	N/A	ENSP00000314783.4
	ENSG00000267968	ENST00000598079.1	TSL:3	n.213+4624G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72947 AN: 151960 Hom.: 18149 Cov.: 33

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.480 AC: 73018 AN: 152078 Hom.: 18183 Cov.: 33 AF XY: 0.482 AC XY: 35805 AN XY: 74346

African (AFR) AF: 0.595 AC: 24690 AN: 41484

American (AMR) AF: 0.370 AC: 5664 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1699 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1425 AN: 5154

South Asian (SAS) AF: 0.412 AC: 1989 AN: 4822

European-Finnish (FIN) AF: 0.501 AC: 5296 AN: 10566

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30513 AN: 67976

Other (OTH) AF: 0.483 AC: 1019 AN: 2108

Alfa AF: 0.473 Hom.: 6060

Bravo AF: 0.478

Asia WGS AF: 0.337 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.88
PhyloP100		-0.67
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: rs2739442; hg19: chr19-51339173; COSMIC: COSV56831526; COSMIC: COSV56831526;