19-50831634-C-T

Variant names:

• chr19-50831634-C-T
• rs3745523
• NM_017509.4:c.-31-111G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017509.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	NM_017509.4	MANE Select	c.-31-111G>A		intron	N/A	NP_059979.2
	KLK15	NM_001277081.2		c.-31-111G>A		intron	N/A	NP_001264010.1	Q9H2R5-5
	KLK15	NM_001277082.2		c.-31-111G>A		intron	N/A	NP_001264011.1	M0R0D7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	ENST00000598239.6	TSL:1 MANE Select	c.-31-111G>A		intron	N/A	ENSP00000469315.1	Q9H2R5-1
	KLK15	ENST00000906215.1		c.-31-111G>A		intron	N/A	ENSP00000576274.1
	KLK15	ENST00000952480.1		c.-31-111G>A		intron	N/A	ENSP00000622539.1

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

African (AFR) AF: 0.316 AC: 2819 AN: 8930

American (AMR) AF: 0.294 AC: 2185 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 1904 AN: 11210

East Asian (EAS) AF: 0.304 AC: 6957 AN: 22862

South Asian (SAS) AF: 0.327 AC: 6455 AN: 19716

European-Finnish (FIN) AF: 0.212 AC: 7242 AN: 34182

Middle Eastern (MID) AF: 0.174 AC: 466 AN: 2678

European-Non Finnish (NFE) AF: 0.254 AC: 70802 AN: 278758

Other (OTH) AF: 0.256 AC: 5699 AN: 22256

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

African (AFR) AF: 0.320 AC: 13244 AN: 41426

American (AMR) AF: 0.265 AC: 4044 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3470

East Asian (EAS) AF: 0.316 AC: 1625 AN: 5146

South Asian (SAS) AF: 0.338 AC: 1626 AN: 4816

European-Finnish (FIN) AF: 0.192 AC: 2031 AN: 10576

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17585 AN: 67902

Other (OTH) AF: 0.233 AC: 491 AN: 2110

Alfa AF: 0.264 Hom.: 20859

Bravo AF: 0.281

Asia WGS AF: 0.324 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.60
PhyloP100		0.21
PromoterAI		0.0012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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