rs2033496

Positions:

• chr19-50835951-C-T

Variant summary

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

The NR_131205.1(LOC105372441):​n.230+4658C>T 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 0.479 in 152,124 control chromosomes in the GnomAD database, including 18,091 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 (18091 hom., cov: 33)
• Consequence: LOC105372441 NR_131205.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

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 = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105372441	NR_131205.1	n.230+4658C>T		intron_variant, non_coding_transcript_variant
LOC105372441	NR_131203.1	n.213+4658C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000598079.1	n.213+4658C>T		intron_variant, non_coding_transcript_variant		3
KLK15	ENST00000326856.8	c.-32+1164G>A		intron_variant		5		ENSP00000314783	A1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72774 AN: 152002 Hom.: 18062 Cov.: 33

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.479 AC: 72840 AN: 152124 Hom.: 18091 Cov.: 33 AF XY: 0.480 AC XY: 35717 AN XY: 74360

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.481

Alfa AF: 0.450 Hom.: 16477

Bravo AF: 0.476

Asia WGS AF: 0.336 AC: 1174 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	7.3
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2033496; hg19: chr19-51339207; COSMIC: COSV56831529; COSMIC: COSV56831529;