Variant 19-50907030-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_004917.5(KLK4):c.669C>T(p.Phe223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,614,132 control chromosomes in the GnomAD database, including 176 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 0.012 ( 19 hom., cov: 32)

Exomes 𝑓: 0.012 ( 157 hom. )

Consequence

KLK4
NM_004917.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.495

Variant links:

Genes affected

KLK4 (HGNC:6365): (kallikrein related peptidase 4) 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 some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Several transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Dec 2014]

KLK4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP7

Synonymous conserved (PhyloP=-0.495 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1776/152268) while in subpopulation NFE AF= 0.0151 (1027/68020). AF 95% confidence interval is 0.0143. There are 19 homozygotes in gnomad4. There are 941 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KLK4	NM_004917.5 linkuse as main transcript	c.669C>T	p.Phe223=	synonymous_variant	6/6	ENST00000324041.6
KLK4	NM_001302961.2 linkuse as main transcript	c.384C>T	p.Phe128=	synonymous_variant	5/5
KLK4	NR_126566.2 linkuse as main transcript	n.658C>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK4	ENST00000324041.6 linkuse as main transcript	c.669C>T	p.Phe223=	synonymous_variant	6/6	1	NM_004917.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1775

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0530

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.0119

AC:

3005

AN:

251476

Hom.:

AF XY:

0.0120

AC XY:

1625

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00619

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.0453

Gnomad NFE exome

AF:

0.0144

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.0118

AC:

17313

AN:

1461864

Hom.:

157

Cov.:

AF XY:

0.0117

AC XY:

8542

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00660

Gnomad4 ASJ exome

AF:

0.00157

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00176

Gnomad4 FIN exome

AF:

0.0466

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.0117

AC:

1776

AN:

152268

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

941

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0530

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.00767

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0142

EpiControl

AF:

0.0122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.6

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over