rs2739442

Positions:

• chr19-50835917-G-A
• chr19-50835917-G-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+4624G>A 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 0.48 in 152,078 control chromosomes in the GnomAD database, including 18,183 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 (18183 hom., cov: 33)
• Consequence: LOC105372441 NR_131205.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105372441	NR_131205.1	n.230+4624G>A		intron_variant, non_coding_transcript_variant
LOC105372441	NR_131203.1	n.213+4624G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000598079.1	n.213+4624G>A		intron_variant, non_coding_transcript_variant		3
KLK15	ENST00000326856.8	c.-32+1198C>T		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72947 AN: 151960 Hom.: 18149 Cov.: 33

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.480 AC: 73018 AN: 152078 Hom.: 18183 Cov.: 33 AF XY: 0.482 AC XY: 35805 AN XY: 74346

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.483

Alfa AF: 0.357 Hom.: 1030

Bravo AF: 0.478

Asia WGS AF: 0.337 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2739442; hg19: chr19-51339173; COSMIC: COSV56831526; COSMIC: COSV56831526;