Variant rs4253301 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000892.5(KLKB1):c.1141T>A(p.Ser381Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S381A) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KLKB1
NM_000892.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.318

Variant links:

Genes affected

KLKB1 (HGNC:6371): (kallikrein B1) This gene encodes a glycoprotein that participates in the surface-dependent activation of blood coagulation, fibrinolysis, kinin generation and inflammation. The encoded preproprotein present in plasma as a non-covalent complex with high molecular weight kininogen undergoes proteolytic processing mediated by activated coagulation factor XII to generate a disulfide-linked, heterodimeric serine protease comprised of heavy and light chains. Certain mutations in this gene cause prekallikrein deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

KLKB1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08109999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLKB1	NM_000892.5 linkuse as main transcript	c.1141T>A	p.Ser381Thr	missense_variant	10/15	ENST00000264690.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KLKB1	ENST00000264690.11 linkuse as main transcript	c.1141T>A	p.Ser381Thr	missense_variant	10/15	1	NM_000892.5	P1
KLKB1	ENST00000511406.5 linkuse as main transcript	n.1202T>A		non_coding_transcript_exon_variant	10/15	1
KLKB1	ENST00000513864.2 linkuse as main transcript	c.1027T>A	p.Ser343Thr	missense_variant	11/15	2
KLKB1	ENST00000467271.1 linkuse as main transcript	n.570T>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250684

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458604

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725870

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.089

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.43

.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-0.64

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.57

N;.

REVEL

Benign

0.20

Sift

Benign

0.14

T;.

Sift4G

Benign

0.32

T;T

Vest4

0.062

MutPred

0.29

Loss of ubiquitination at K386 (P = 0.0935);.;

MVP

0.54

MPC

0.30

ClinPred

0.059

GERP RS

-2.6

gMVP

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over