Variant rs698078 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001102416.3(KNG1):c.1126-84A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,236,656 control chromosomes in the GnomAD database, including 104,173 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 0.43 ( 14689 hom., cov: 33)

Exomes 𝑓: 0.40 ( 89484 hom. )

Consequence

KNG1
NM_001102416.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0820

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KNG1	NM_001102416.3 linkuse as main transcript	c.1126-84A>G	intron_variant	ENST00000644859.2	NP_001095886.1
KNG1	NM_000893.4 linkuse as main transcript	c.1126-84A>G	intron_variant		NP_000884.1
KNG1	NM_001166451.2 linkuse as main transcript	c.1018-84A>G	intron_variant		NP_001159923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KNG1	ENST00000644859.2 linkuse as main transcript	c.1126-84A>G		intron_variant			NM_001102416.3	ENSP00000493985		P01042-1
HRG-AS1	ENST00000630178.2 linkuse as main transcript	n.135+2265T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66046

AN:

151984

Hom.:

14670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.516

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.443

GnomAD4 exome

AF:

0.403

AC:

437485

AN:

1084554

Hom.:

89484

AF XY:

0.403

AC XY:

220694

AN XY:

547686

show subpopulations

Gnomad4 AFR exome

AF:

0.523

Gnomad4 AMR exome

AF:

0.467

Gnomad4 ASJ exome

AF:

0.513

Gnomad4 EAS exome

AF:

0.286

Gnomad4 SAS exome

AF:

0.375

Gnomad4 FIN exome

AF:

0.376

Gnomad4 NFE exome

AF:

0.403

Gnomad4 OTH exome

AF:

0.415

GnomAD4 genome

AF:

0.435

AC:

66116

AN:

152102

Hom.:

14689

Cov.:

AF XY:

0.432

AC XY:

32114

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.516

Gnomad4 AMR

AF:

0.446

Gnomad4 ASJ

AF:

0.513

Gnomad4 EAS

AF:

0.290

Gnomad4 SAS

AF:

0.357

Gnomad4 FIN

AF:

0.367

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.439

Alfa

AF:

0.427

Hom.:

3382

Bravo

AF:

0.447

Asia WGS

AF:

0.354

AC:

1233

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.7

DANN

Benign

0.53

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