3-186743735-C-A
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_000893.4(KNG1):c.1234C>A(p.Arg412Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
KNG1
NM_000893.4 synonymous
NM_000893.4 synonymous
Scores
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.776
Publications
24 publications found
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]
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new If you want to explore the variant's impact on the transcript NM_000893.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP7
Synonymous conserved (PhyloP=0.776 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000893.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KNG1 | MANE Select | c.*1404C>A | 3_prime_UTR | Exon 10 of 10 | NP_001095886.1 | P01042-1 | |||
| KNG1 | c.1234C>A | p.Arg412Arg | synonymous | Exon 11 of 11 | NP_000884.1 | P01042-2 | |||
| KNG1 | c.1126C>A | p.Arg376Arg | synonymous | Exon 10 of 10 | NP_001159923.1 | P01042-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KNG1 | TSL:1 | c.1234C>A | p.Arg412Arg | synonymous | Exon 11 of 11 | ENSP00000287611.2 | P01042-2 | ||
| KNG1 | MANE Select | c.*1404C>A | 3_prime_UTR | Exon 10 of 10 | ENSP00000493985.1 | P01042-1 | |||
| KNG1 | TSL:3 | c.1126C>A | p.Arg376Arg | synonymous | Exon 10 of 10 | ENSP00000396025.1 | P01042-3 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152140Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152140
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
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Gnomad ASJ
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD2 exomes AF: 0.00000398 AC: 1AN: 250976 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250976
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461638Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727136 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461638
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
727136
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33476
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86244
European-Finnish (FIN)
AF:
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111798
Other (OTH)
AF:
AC:
0
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000131 AC: 2AN: 152140Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74314 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152140
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74314
show subpopulations
African (AFR)
AF:
AC:
2
AN:
41434
American (AMR)
AF:
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5194
South Asian (SAS)
AF:
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
10604
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68024
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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