19-50833083-C-T

Position:

• chr19-50833083-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.-32+444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,292 control chromosomes in the GnomAD database, including 3,279 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 0.20 (3277 hom., cov: 32)
  • Exomes 𝑓: 0.19 (2 hom.)
• Consequence: KLK15 NM_017509.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK15	NM_017509.4	c.-32+444G>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.-32+444G>A		intron_variant		1	NM_017509.4	ENSP00000469315.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30486 AN: 152062 Hom.: 3277 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.188 AC: 21 AN: 112 Hom.: 2 Cov.: 0 AF XY: 0.188 AC XY: 15 AN XY: 80

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.200 AC: 30488 AN: 152180 Hom.: 3277 Cov.: 32 AF XY: 0.194 AC XY: 14452 AN XY: 74412

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.0898

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.177

Alfa AF: 0.179 Hom.: 1923

Bravo AF: 0.207

Asia WGS AF: 0.168 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.22

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs266851; hg19: chr19-51336339;