dbSNP rs1624230: KNG1:c.306+931C>A (chr3-186721146-C-A) – 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.306+931C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,800 control chromosomes in the GnomAD database, including 13,955 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 0.42 ( 13955 hom., cov: 31)

Exomes 𝑓: 0.30 ( 0 hom. )

Consequence

KNG1
NM_001102416.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.28

Publications

11 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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.592 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.306+931C>A	intron	N/A	NP_001095886.1	P01042-1
KNG1	NM_000893.4		c.306+931C>A	intron	N/A	NP_000884.1	P01042-2
KNG1	NM_001166451.2		c.306+931C>A	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.306+931C>A	intron	N/A	ENSP00000493985.1	P01042-1
KNG1	ENST00000287611.8	TSL:1	c.306+931C>A	intron	N/A	ENSP00000287611.2	P01042-2
KNG1	ENST00000897809.1		c.306+931C>A	intron	N/A	ENSP00000567868.1

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64155

AN:

151672

Hom.:

13949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.612

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.401

GnomAD4 exome

AF:

0.300

AC:

AN:

Hom.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.423

AC:

64198

AN:

151790

Hom.:

13955

Cov.:

AF XY:

0.422

AC XY:

31342

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.484

AC:

20009

AN:

41318

American (AMR)

AF:

0.357

AC:

5452

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1266

AN:

3470

East Asian (EAS)

AF:

0.410

AC:

2114

AN:

5152

South Asian (SAS)

AF:

0.610

AC:

2931

AN:

4802

European-Finnish (FIN)

AF:

0.385

AC:

4071

AN:

10564

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.396

AC:

26905

AN:

67918

Other (OTH)

AF:

0.400

AC:

843

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1852

3704

5555

7407

9259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.402

Hom.:

34601

Bravo

AF:

0.417

Asia WGS

AF:

0.509

AC:

1769

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.3

(source)

DANN

Benign

0.72

PhyloP100

-1.3

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