chr19-50833976-T-C

Position:

• chr19-50833976-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105372441	NR_131203.1	n.213+2683T>C		intron_variant
LOC105372441	NR_131205.1	n.230+2683T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK15	ENST00000695965.1	c.-481A>G		5_prime_UTR_variant	1/5			ENSP00000512291.1
KLK15	ENST00000326856.8	c.-31-2453A>G		intron_variant		5		ENSP00000314783.4
ENSG00000267968	ENST00000598079.1	n.213+2683T>C		intron_variant		3

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

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.456

Alfa AF: 0.452 Hom.: 3099

Bravo AF: 0.413

Asia WGS AF: 0.513 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2659055; hg19: chr19-51337232;