Variant 3-186720155-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001102416.3(KNG1):c.246T>C(p.Asp82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,612,260 control chromosomes in the GnomAD database, including 11,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 913 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10428 hom. )

Consequence

KNG1
NM_001102416.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.44

Variant links:

Genes affected

KNG1 (HGNC:6383): (kininogen 1) This gene uses alternative splicing to generate two different proteins- high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK). HMWK is essential for blood coagulation and assembly of the kallikrein-kinin system. Also, bradykinin, a peptide causing numerous physiological effects, is released from HMWK. Bradykinin also functions as an antimicrobial peptide with antibacterial and antifungal activity. In contrast to HMWK, LMWK is not involved in blood coagulation. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reduces or depletes angiotensin converting enzyme 2 (ACE2), which results in an increase in levels of des-Arg(9)-bradykinin, a bioactive metabolite of bradykinin that is associated with lung injury and inflammation. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2020]

KNG1 links:

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

HRG-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-186720155-T-C is Benign according to our data. Variant chr3-186720155-T-C is described in ClinVar as [Benign]. Clinvar id is 3059701.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KNG1	NM_001102416.3 linkuse as main transcript	c.246T>C	p.Asp82=	synonymous_variant	2/10	ENST00000644859.2	NP_001095886.1
KNG1	NM_000893.4 linkuse as main transcript	c.246T>C	p.Asp82=	synonymous_variant	2/11		NP_000884.1
KNG1	NM_001166451.2 linkuse as main transcript	c.246T>C	p.Asp82=	synonymous_variant	2/10		NP_001159923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KNG1	ENST00000644859.2 linkuse as main transcript	c.246T>C	p.Asp82=	synonymous_variant	2/10		NM_001102416.3	ENSP00000493985		P01042-1
HRG-AS1	ENST00000630178.2 linkuse as main transcript	n.136-1586A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

16009

AN:

152002

Hom.:

914

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0765

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0841

Gnomad EAS

AF:

0.0522

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.0886

GnomAD3 exomes

AF:

0.121

AC:

30531

AN:

251286

Hom.:

2018

AF XY:

0.121

AC XY:

16508

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0701

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.0919

Gnomad EAS exome

AF:

0.0594

Gnomad SAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.116

AC:

169160

AN:

1460140

Hom.:

10428

Cov.:

AF XY:

0.117

AC XY:

84651

AN XY:

726442

show subpopulations

Gnomad4 AFR exome

AF:

0.0706

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.0911

Gnomad4 EAS exome

AF:

0.0373

Gnomad4 SAS exome

AF:

0.141

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.105

AC:

16020

AN:

152120

Hom.:

913

Cov.:

AF XY:

0.106

AC XY:

7871

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0764

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0841

Gnomad4 EAS

AF:

0.0521

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.0891

Alfa

AF:

0.111

Hom.:

1285

Bravo

AF:

0.101

Asia WGS

AF:

0.0940

AC:

326

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.107

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KNG1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.7

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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