rs4253252

Variant summary

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

The NM_000892.5(KLKB1):​c.329-477T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,996 control chromosomes in the GnomAD database, including 24,148 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 0.56 ( 24148 hom., cov: 32)

Consequence

KLKB1
NM_000892.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.691
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]

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 (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KLKB1NM_000892.5 linkuse as main transcriptc.329-477T>G intron_variant ENST00000264690.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KLKB1ENST00000264690.11 linkuse as main transcriptc.329-477T>G intron_variant 1 NM_000892.5 P1

Frequencies

GnomAD3 genomes
AF:
0.559
AC:
84927
AN:
151878
Hom.:
24117
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.639
Gnomad AMI
AF:
0.604
Gnomad AMR
AF:
0.575
Gnomad ASJ
AF:
0.444
Gnomad EAS
AF:
0.681
Gnomad SAS
AF:
0.399
Gnomad FIN
AF:
0.583
Gnomad MID
AF:
0.547
Gnomad NFE
AF:
0.511
Gnomad OTH
AF:
0.552
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.559
AC:
85010
AN:
151996
Hom.:
24148
Cov.:
32
AF XY:
0.559
AC XY:
41544
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.639
Gnomad4 AMR
AF:
0.576
Gnomad4 ASJ
AF:
0.444
Gnomad4 EAS
AF:
0.680
Gnomad4 SAS
AF:
0.400
Gnomad4 FIN
AF:
0.583
Gnomad4 NFE
AF:
0.511
Gnomad4 OTH
AF:
0.554
Alfa
AF:
0.520
Hom.:
18331
Bravo
AF:
0.568
Asia WGS
AF:
0.525
AC:
1826
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.81
DANN
Benign
0.57

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.

Other links and lift over

dbSNP: rs4253252; hg19: chr4-187157458; API