chr19-50831634-C-T

Position:

• chr19-50831634-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017509.4(KLK15):​c.-31-111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 559,944 control chromosomes in the GnomAD database, including 19,953 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 0.27 (5752 hom., cov: 30)
  • Exomes 𝑓: 0.26 (14201 hom.)
• Consequence: KLK15 NM_017509.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK15	NM_017509.4	c.-31-111G>A		intron_variant		ENST00000598239.6	NP_059979.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK15	ENST00000598239.6	c.-31-111G>A		intron_variant		1	NM_017509.4	ENSP00000469315.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41407 AN: 151800 Hom.: 5737 Cov.: 30

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.256 AC: 104529 AN: 408026 Hom.: 14201 AF XY: 0.258 AC XY: 53492 AN XY: 207452

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.256

GnomAD4 genome AF: 0.273 AC: 41452 AN: 151918 Hom.: 5752 Cov.: 30 AF XY: 0.269 AC XY: 19988 AN XY: 74262

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.233

Alfa AF: 0.258 Hom.: 8857

Bravo AF: 0.281

Asia WGS AF: 0.324 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3745523; hg19: chr19-51334890; COSMIC: COSV56832355; COSMIC: COSV56832355;