dbSNP rs1654552: KLK4:p.Ser22Ser (chr19-50909410-C-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004917.5(KLK4):c.66G>T(p.Ser22Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,613,460 control chromosomes in the GnomAD database, including 156,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 11458 hom., cov: 32)

Exomes 𝑓: 0.44 ( 145226 hom. )

Consequence

KLK4
NM_004917.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.425

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 19-50909410-C-A is Benign according to our data. Variant chr19-50909410-C-A is described in ClinVar as [Benign]. Clinvar id is 259565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50909410-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK4	NM_004917.5 link	c.66G>T	p.Ser22Ser	synonymous_variant	Exon 3 of 6	ENST00000324041.6	NP_004908.4	Q9Y5K2A0A0C4DFQ5
KLK4	XM_011527545.4 link	c.66G>T	p.Ser22Ser	synonymous_variant	Exon 2 of 4		XP_011525847.1
KLK4	NM_001302961.2 link	c.-232G>T		5_prime_UTR_variant	Exon 2 of 5		NP_001289890.1	Q9Y5K2Q5BQA0
KLK4	NR_126566.2 link	n.62-15G>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6 link	c.66G>T	p.Ser22Ser	synonymous_variant	Exon 3 of 6	1	NM_004917.5	ENSP00000326159.1		A0A0C4DFQ5

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53261

AN:

151978

Hom.:

11460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.452

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.400

AC:

100373

AN:

250952

Hom.:

22202

AF XY:

0.402

AC XY:

54572

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.463

Gnomad ASJ exome

AF:

0.468

Gnomad EAS exome

AF:

0.118

Gnomad SAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.474

Gnomad NFE exome

AF:

0.471

Gnomad OTH exome

AF:

0.440

GnomAD4 exome

AF:

0.436

AC:

637077

AN:

1461364

Hom.:

145226

Cov.:

AF XY:

0.434

AC XY:

315690

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.457

Gnomad4 ASJ exome

AF:

0.463

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.313

Gnomad4 FIN exome

AF:

0.476

Gnomad4 NFE exome

AF:

0.465

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.350

AC:

53267

AN:

152096

Hom.:

11458

Cov.:

AF XY:

0.352

AC XY:

26177

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.431

Gnomad4 ASJ

AF:

0.449

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.489

Gnomad4 NFE

AF:

0.469

Gnomad4 OTH

AF:

0.364

Alfa

AF:

0.417

Hom.:

8038

Bravo

AF:

0.336

Asia WGS

AF:

0.184

AC:

643

AN:

3478

EpiCase

AF:

0.471

EpiControl

AF:

0.470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.7

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: -21

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