dbSNP rs710448: KNG1:c.930+2422A>G (chr3-186735096-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001102416.3(KNG1):c.930+2422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,098 control chromosomes in the GnomAD database, including 10,686 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 0.37 ( 10686 hom., cov: 32)

Consequence

KNG1
NM_001102416.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102416.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KNG1	NM_001102416.3	MANE Select	c.930+2422A>G	intron	N/A	NP_001095886.1	P01042-1
KNG1	NM_000893.4		c.930+2422A>G	intron	N/A	NP_000884.1	P01042-2
KNG1	NM_001166451.2		c.822+2422A>G	intron	N/A	NP_001159923.1	P01042-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KNG1	ENST00000644859.2	MANE Select	c.930+2422A>G	intron	N/A	ENSP00000493985.1	P01042-1
KNG1	ENST00000287611.8	TSL:1	c.930+2422A>G	intron	N/A	ENSP00000287611.2	P01042-2
KNG1	ENST00000897809.1		c.960+2422A>G	intron	N/A	ENSP00000567868.1

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56668

AN:

151980

Hom.:

10685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.580

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.363

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.373

AC:

56708

AN:

152098

Hom.:

10686

Cov.:

AF XY:

0.371

AC XY:

27544

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.379

AC:

15744

AN:

41492

American (AMR)

AF:

0.326

AC:

4981

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1166

AN:

3468

East Asian (EAS)

AF:

0.340

AC:

1761

AN:

5176

South Asian (SAS)

AF:

0.478

AC:

2306

AN:

4826

European-Finnish (FIN)

AF:

0.364

AC:

3844

AN:

10562

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.375

AC:

25503

AN:

67986

Other (OTH)

AF:

0.363

AC:

768

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1850

3700

5551

7401

9251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.391

Hom.:

1777

Bravo

AF:

0.367

Asia WGS

AF:

0.417

AC:

1451

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.9

(source)

DANN

Benign

0.46

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over