Variant 19-50820420-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002257.4(KLK1):c.230G>A(p.Arg77His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 1,609,342 control chromosomes in the GnomAD database, including 1,292 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

Frequency

Genomes: 𝑓 0.050 ( 249 hom., cov: 28)

Exomes 𝑓: 0.034 ( 1043 hom. )

Consequence

KLK1
NM_002257.4 missense

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: -0.174

Variant links:

Genes affected

KLK1 (HGNC:6357): (kallikrein 1) 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. This protein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. [provided by RefSeq, Jul 2008]

KLK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0102929175).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK1	NM_002257.4 linkuse as main transcript	c.230G>A	p.Arg77His	missense_variant	3/5	ENST00000301420.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK1	ENST00000301420.3 linkuse as main transcript	c.230G>A	p.Arg77His	missense_variant	3/5	1	NM_002257.4	P1	P06870-1
KLK1	ENST00000593859.5 linkuse as main transcript	n.269G>A		non_coding_transcript_exon_variant	3/4	2
KLK1	ENST00000596300.1 linkuse as main transcript	n.430G>A		non_coding_transcript_exon_variant	1/3	2
KLK1	ENST00000593325.5 linkuse as main transcript	c.*1039G>A		3_prime_UTR_variant, NMD_transcript_variant	4/6	2

Frequencies

GnomAD3 genomes

AF:

0.0496

AC:

7431

AN:

149908

Hom.:

248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0998

Gnomad AMI

AF:

0.0429

Gnomad AMR

AF:

0.0412

Gnomad ASJ

AF:

0.0315

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.00698

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0351

Gnomad OTH

AF:

0.0513

GnomAD3 exomes

AF:

0.0312

AC:

7765

AN:

248920

Hom.:

207

AF XY:

0.0301

AC XY:

4044

AN XY:

134486

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0267

Gnomad ASJ exome

AF:

0.0230

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.00742

Gnomad NFE exome

AF:

0.0370

Gnomad OTH exome

AF:

0.0389

GnomAD4 exome

AF:

0.0341

AC:

49813

AN:

1459322

Hom.:

1043

Cov.:

AF XY:

0.0332

AC XY:

24114

AN XY:

725686

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.0276

Gnomad4 ASJ exome

AF:

0.0237

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0140

Gnomad4 FIN exome

AF:

0.00877

Gnomad4 NFE exome

AF:

0.0364

Gnomad4 OTH exome

AF:

0.0353

GnomAD4 genome

AF:

0.0496

AC:

7440

AN:

150020

Hom.:

249

Cov.:

AF XY:

0.0468

AC XY:

3414

AN XY:

73014

show subpopulations

Gnomad4 AFR

AF:

0.0997

Gnomad4 AMR

AF:

0.0411

Gnomad4 ASJ

AF:

0.0315

Gnomad4 EAS

AF:

0.000198

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.00698

Gnomad4 NFE

AF:

0.0351

Gnomad4 OTH

AF:

0.0507

Alfa

AF:

0.0381

Hom.:

251

Bravo

AF:

0.0549

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0309

AC:

119

ESP6500AA

AF:

0.0971

AC:

428

ESP6500EA

AF:

0.0360

AC:

310

ExAC

AF:

0.0331

AC:

4017

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0380

EpiControl

AF:

0.0404

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Kallikrein, decreased urinary activity of

Other:1

Affects, no assertion criteria provided

literature only

OMIM

Mar 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.22

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.36

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.97

MutationTaster

Benign

2.0e-11

A;A

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.27

Sift

Uncertain

0.010

Sift4G

Benign

0.12

Polyphen

0.81

Vest4

0.13

MPC

0.54

ClinPred

0.027

GERP RS

-0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.56

gMVP

0.31

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