rs190552

Positions:

• chr19-50834937-T-C

Variant summary

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

The NR_131205.1(LOC105372441):​n.230+3644T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,094 control chromosomes in the GnomAD database, including 4,815 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 0.24 (4815 hom., cov: 31)
• Consequence: LOC105372441 NR_131205.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.660

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105372441	NR_131205.1	n.230+3644T>C		intron_variant, non_coding_transcript_variant
LOC105372441	NR_131203.1	n.213+3644T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000598079.1	n.213+3644T>C		intron_variant, non_coding_transcript_variant		3
KLK15	ENST00000326856.8	c.-32+2178A>G		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37200 AN: 151976 Hom.: 4814 Cov.: 31

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.245 AC: 37216 AN: 152094 Hom.: 4815 Cov.: 31 AF XY: 0.245 AC XY: 18183 AN XY: 74354

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.273

Alfa AF: 0.234 Hom.: 878

Bravo AF: 0.250

Asia WGS AF: 0.143 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.0
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs190552; hg19: chr19-51338193;