Variant 3-186722454-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001102416.3(KNG1):c.324G>A(p.Thr108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,609,830 control chromosomes in the GnomAD database, including 79,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 6375 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73406 hom. )

Consequence

KNG1
NM_001102416.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.346

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 3-186722454-G-A is Benign according to our data. Variant chr3-186722454-G-A is described in ClinVar as [Benign]. Clinvar id is 3059276.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.346 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KNG1	NM_001102416.3 linkuse as main transcript	c.324G>A	p.Thr108=	synonymous_variant	3/10	ENST00000644859.2
KNG1	NM_000893.4 linkuse as main transcript	c.324G>A	p.Thr108=	synonymous_variant	3/11
KNG1	NM_001166451.2 linkuse as main transcript	c.324G>A	p.Thr108=	synonymous_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KNG1	ENST00000644859.2 linkuse as main transcript	c.324G>A	p.Thr108=	synonymous_variant	3/10		NM_001102416.3		P01042-1
HRG-AS1	ENST00000630178.2 linkuse as main transcript	n.136-3885C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42228

AN:

151946

Hom.:

6365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.354

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.316

GnomAD3 exomes

AF:

0.308

AC:

77154

AN:

250232

Hom.:

12483

AF XY:

0.305

AC XY:

41302

AN XY:

135250

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.420

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.228

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.335

GnomAD4 exome

AF:

0.313

AC:

456316

AN:

1457766

Hom.:

73406

Cov.:

AF XY:

0.311

AC XY:

225598

AN XY:

725342

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.414

Gnomad4 ASJ exome

AF:

0.351

Gnomad4 EAS exome

AF:

0.223

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.324

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.278

AC:

42263

AN:

152064

Hom.:

6375

Cov.:

AF XY:

0.278

AC XY:

20663

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.165

Gnomad4 AMR

AF:

0.355

Gnomad4 ASJ

AF:

0.366

Gnomad4 EAS

AF:

0.224

Gnomad4 SAS

AF:

0.207

Gnomad4 FIN

AF:

0.306

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.315

Alfa

AF:

0.323

Hom.:

9134

Bravo

AF:

0.282

Asia WGS

AF:

0.232

AC:

808

AN:

3478

EpiCase

AF:

0.338

EpiControl

AF:

0.341

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KNG1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

-0.78

CADD

Benign

1.5

DANN

Benign

0.82

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