Variant chr4-186228386-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000892.5(KLKB1):c.58+133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 679,390 control chromosomes in the GnomAD database, including 95,899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24245 hom., cov: 31)

Exomes 𝑓: 0.52 ( 71654 hom. )

Consequence

KLKB1
NM_000892.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.140

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 4-186228386-G-A is Benign according to our data. Variant chr4-186228386-G-A is described in ClinVar as [Benign]. Clinvar id is 1263748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLKB1	NM_000892.5 linkuse as main transcript	c.58+133G>A		intron_variant		ENST00000264690.11	NP_000883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLKB1	ENST00000264690.11 linkuse as main transcript	c.58+133G>A		intron_variant		1	NM_000892.5	ENSP00000264690	P1

Frequencies

GnomAD3 genomes

AF:

0.561

AC:

85076

AN:

151754

Hom.:

24215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.603

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.681

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.554

GnomAD4 exome

AF:

0.515

AC:

271689

AN:

527518

Hom.:

71654

AF XY:

0.504

AC XY:

143664

AN XY:

284818

show subpopulations

Gnomad4 AFR exome

AF:

0.650

Gnomad4 AMR exome

AF:

0.615

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.639

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.576

Gnomad4 NFE exome

AF:

0.506

Gnomad4 OTH exome

AF:

0.530

GnomAD4 genome

AF:

0.561

AC:

85158

AN:

151872

Hom.:

24245

Cov.:

AF XY:

0.560

AC XY:

41588

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.645

Gnomad4 AMR

AF:

0.577

Gnomad4 ASJ

AF:

0.444

Gnomad4 EAS

AF:

0.680

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.582

Gnomad4 NFE

AF:

0.510

Gnomad4 OTH

AF:

0.555

Alfa

AF:

0.504

Hom.:

38419

Bravo

AF:

0.570

Asia WGS

AF:

0.524

AC:

1823

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.51

DANN

Benign

0.44

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