Genetic Variant KLK15:c.-32+444G>A (chr19-50833083-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017509.4(KLK15):c.-32+444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,292 control chromosomes in the GnomAD database, including 3,279 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 0.20 ( 3277 hom., cov: 32)

Exomes 𝑓: 0.19 ( 2 hom. )

Consequence

KLK15
NM_017509.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.816

Publications

9 publications found

Variant links:

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]

KLK15 links:

ENSG00000267968 (HGNC:):

ENSG00000267968 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK15	NM_017509.4 link	c.-32+444G>A		intron_variant	Intron 1 of 5	ENST00000598239.6	NP_059979.2	Q9H2R5-1Q6UBM2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK15	ENST00000598239.6 link	c.-32+444G>A		intron_variant	Intron 1 of 5	1	NM_017509.4	ENSP00000469315.1		Q9H2R5-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30486

AN:

152062

Hom.:

3277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.0898

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.178

GnomAD4 exome

AF:

0.188

AC:

AN:

112

Hom.:

Cov.:

AF XY:

0.188

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.193

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.200

AC:

30488

AN:

152180

Hom.:

3277

Cov.:

AF XY:

0.194

AC XY:

14452

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.279

AC:

11595

AN:

41500

American (AMR)

AF:

0.147

AC:

2254

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

510

AN:

3466

East Asian (EAS)

AF:

0.120

AC:

618

AN:

5170

South Asian (SAS)

AF:

0.221

AC:

1066

AN:

4816

European-Finnish (FIN)

AF:

0.0898

AC:

953

AN:

10612

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12900

AN:

68002

Other (OTH)

AF:

0.177

AC:

373

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1273

2545

3818

5090

6363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.182

Hom.:

2331

Bravo

AF:

0.207

Asia WGS

AF:

0.168

AC:

582

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.0

(source)

DANN

Benign

0.22

PhyloP100

-0.82

PromoterAI

-0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over