Variant rs1054713 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002257.4(KLK1):c.405T>C(p.Asp135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,613,394 control chromosomes in the GnomAD database, including 375,506 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 0.70 ( 37461 hom., cov: 30)

Exomes 𝑓: 0.68 ( 338045 hom. )

Consequence

KLK1
NM_002257.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.10

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:

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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=-0.93).

BP7

Synonymous conserved (PhyloP=-5.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 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.405T>C	p.Asp135=	synonymous_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.405T>C	p.Asp135=	synonymous_variant	3/5	1	NM_002257.4	P1	P06870-1
KLK1	ENST00000593859.5 linkuse as main transcript	n.444T>C		non_coding_transcript_exon_variant	3/4	2
KLK1	ENST00000596300.1 linkuse as main transcript	n.605T>C		non_coding_transcript_exon_variant	1/3	2
KLK1	ENST00000593325.5 linkuse as main transcript	c.*1214T>C		3_prime_UTR_variant, NMD_transcript_variant	4/6	2

Frequencies

GnomAD3 genomes

AF:

0.700

AC:

106220

AN:

151704

Hom.:

37413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.740

Gnomad ASJ

AF:

0.629

Gnomad EAS

AF:

0.795

Gnomad SAS

AF:

0.654

Gnomad FIN

AF:

0.663

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.701

GnomAD3 exomes

AF:

0.696

AC:

174911

AN:

251386

Hom.:

61547

AF XY:

0.686

AC XY:

93248

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.749

Gnomad AMR exome

AF:

0.806

Gnomad ASJ exome

AF:

0.618

Gnomad EAS exome

AF:

0.792

Gnomad SAS exome

AF:

0.625

Gnomad FIN exome

AF:

0.670

Gnomad NFE exome

AF:

0.671

Gnomad OTH exome

AF:

0.678

GnomAD4 exome

AF:

0.678

AC:

991520

AN:

1461572

Hom.:

338045

Cov.:

AF XY:

0.676

AC XY:

491301

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.741

Gnomad4 AMR exome

AF:

0.795

Gnomad4 ASJ exome

AF:

0.615

Gnomad4 EAS exome

AF:

0.782

Gnomad4 SAS exome

AF:

0.631

Gnomad4 FIN exome

AF:

0.673

Gnomad4 NFE exome

AF:

0.674

Gnomad4 OTH exome

AF:

0.676

GnomAD4 genome

AF:

0.700

AC:

106326

AN:

151822

Hom.:

37461

Cov.:

AF XY:

0.698

AC XY:

51784

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.745

Gnomad4 AMR

AF:

0.740

Gnomad4 ASJ

AF:

0.629

Gnomad4 EAS

AF:

0.795

Gnomad4 SAS

AF:

0.654

Gnomad4 FIN

AF:

0.663

Gnomad4 NFE

AF:

0.671

Gnomad4 OTH

AF:

0.704

Alfa

AF:

0.667

Hom.:

44275

Bravo

AF:

0.712

Asia WGS

AF:

0.721

AC:

2507

AN:

3478

EpiCase

AF:

0.662

EpiControl

AF:

0.659

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.017

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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