Variant rs2242670 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004917.5(KLK4):c.224+193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,477,836 control chromosomes in the GnomAD database, including 206,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.51 ( 20305 hom., cov: 30)

Exomes 𝑓: 0.53 ( 186073 hom. )

Consequence

KLK4
NM_004917.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.43

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 19-50909059-A-G is Benign according to our data. Variant chr19-50909059-A-G is described in ClinVar as [Benign]. Clinvar id is 1253084.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
KLK4	NM_004917.5 linkuse as main transcript	c.224+193T>C	intron_variant	ENST00000324041.6
KLK4	NM_001302961.2 linkuse as main transcript	c.-62+181T>C	intron_variant
KLK4	XM_011527545.4 linkuse as main transcript	c.224+193T>C	intron_variant
KLK4	NR_126566.2 linkuse as main transcript	n.217+181T>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK4	ENST00000324041.6 linkuse as main transcript	c.224+193T>C		intron_variant		1	NM_004917.5	P1

Frequencies

GnomAD3 genomes

AF:

0.511

AC:

77490

AN:

151664

Hom.:

20285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.482

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.518

Gnomad ASJ

AF:

0.534

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.548

Gnomad OTH

AF:

0.503

GnomAD4 exome

AF:

0.525

AC:

696497

AN:

1326054

Hom.:

186073

Cov.:

AF XY:

0.524

AC XY:

338471

AN XY:

646428

show subpopulations

Gnomad4 AFR exome

AF:

0.486

Gnomad4 AMR exome

AF:

0.517

Gnomad4 ASJ exome

AF:

0.546

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.429

Gnomad4 FIN exome

AF:

0.561

Gnomad4 NFE exome

AF:

0.543

Gnomad4 OTH exome

AF:

0.521

GnomAD4 genome

AF:

0.511

AC:

77579

AN:

151782

Hom.:

20305

Cov.:

AF XY:

0.511

AC XY:

37915

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.482

Gnomad4 AMR

AF:

0.518

Gnomad4 ASJ

AF:

0.534

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.400

Gnomad4 FIN

AF:

0.567

Gnomad4 NFE

AF:

0.548

Gnomad4 OTH

AF:

0.504

Alfa

AF:

0.541

Hom.:

29742

Bravo

AF:

0.507

Asia WGS

AF:

0.317

AC:

1106

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.52

DANN

Benign

0.45

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over