ENST00000601680.1:n.1149G>A

Variant names:

• chr19-50825538-C-T
• rs3212853
• ENST00000601680.1:n.1149G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000601680.1(KLK15):​n.1149G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 349,582 control chromosomes in the GnomAD database, including 173 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 0.025 (64 hom., cov: 32)
  • Exomes 𝑓: 0.027 (109 hom.)
• Consequence: KLK15 ENST00000601680.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0246 (3742/152228) while in subpopulation NFE AF = 0.0368 (2505/68008). AF 95% confidence interval is 0.0356. There are 64 homozygotes in GnomAd4. There are 1734 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000601680.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	NM_017509.4	MANE Select	c.*258G>A		3_prime_UTR	Exon 6 of 6	NP_059979.2
	KLK15	NR_102274.1		n.939G>A		non_coding_transcript_exon	Exon 5 of 5
	KLK15	NM_001277081.2		c.*258G>A		3_prime_UTR	Exon 6 of 6	NP_001264010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	ENST00000601680.1	TSL:1	n.1149G>A		non_coding_transcript_exon	Exon 4 of 4
	KLK15	ENST00000598239.6	TSL:1 MANE Select	c.*258G>A		3_prime_UTR	Exon 6 of 6	ENSP00000469315.1
	KLK15	ENST00000695963.1		n.757G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3741 AN: 152112 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.00669

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0368

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.0274 AC: 5404 AN: 197354 Hom.: 109 Cov.: 2 AF XY: 0.0267 AC XY: 2695 AN XY: 101072

African (AFR) AF: 0.00684 AC: 44 AN: 6436

American (AMR) AF: 0.0278 AC: 208 AN: 7490

Ashkenazi Jewish (ASJ) AF: 0.0322 AC: 221 AN: 6872

East Asian (EAS) AF: 0.00 AC: 0 AN: 14052

South Asian (SAS) AF: 0.00525 AC: 71 AN: 13522

European-Finnish (FIN) AF: 0.0187 AC: 239 AN: 12802

Middle Eastern (MID) AF: 0.0325 AC: 32 AN: 984

European-Non Finnish (NFE) AF: 0.0345 AC: 4236 AN: 122850

Other (OTH) AF: 0.0286 AC: 353 AN: 12346

GnomAD4 genome AF: 0.0246 AC: 3742 AN: 152228 Hom.: 64 Cov.: 32 AF XY: 0.0233 AC XY: 1734 AN XY: 74424

African (AFR) AF: 0.00667 AC: 277 AN: 41550

American (AMR) AF: 0.0353 AC: 540 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00581 AC: 28 AN: 4816

European-Finnish (FIN) AF: 0.0127 AC: 134 AN: 10592

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0368 AC: 2505 AN: 68008

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0333 Hom.: 213

Bravo AF: 0.0257

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.79
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3212853; hg19: chr19-51328794;