rs5030093

Variant names:

• chr3-186743302-G-A
• rs5030093
• NM_001102416.3:c.*971G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001102416.3(KNG1):​c.*971G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 182,734 control chromosomes in the GnomAD database, including 5,538 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 0.25 (4733 hom., cov: 33)
  • Exomes 𝑓: 0.22 (805 hom.)
• Consequence: KNG1 NM_001102416.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933
• Publications: 4 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]

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KNG1	NM_001102416.3	MANE Select	c.*971G>A		3_prime_UTR	Exon 10 of 10	NP_001095886.1	P01042-1
	KNG1	NM_000893.4		c.1204-403G>A		intron	N/A	NP_000884.1	P01042-2
	KNG1	NM_001166451.2		c.1096-403G>A		intron	N/A	NP_001159923.1	P01042-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KNG1	ENST00000644859.2	MANE Select	c.*971G>A		3_prime_UTR	Exon 10 of 10	ENSP00000493985.1	P01042-1
	KNG1	ENST00000287611.8	TSL:1	c.1204-403G>A		intron	N/A	ENSP00000287611.2	P01042-2
	KNG1	ENST00000897802.1		c.*971G>A		3_prime_UTR	Exon 9 of 9	ENSP00000567861.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37662 AN: 151986 Hom.: 4728 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.218 AC: 6664 AN: 30630 Hom.: 805 Cov.: 0 AF XY: 0.219 AC XY: 3496 AN XY: 15976

African (AFR) AF: 0.260 AC: 171 AN: 658

American (AMR) AF: 0.243 AC: 700 AN: 2886

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 105 AN: 706

East Asian (EAS) AF: 0.136 AC: 267 AN: 1968

South Asian (SAS) AF: 0.190 AC: 693 AN: 3644

European-Finnish (FIN) AF: 0.258 AC: 308 AN: 1194

Middle Eastern (MID) AF: 0.261 AC: 23 AN: 88

European-Non Finnish (NFE) AF: 0.226 AC: 4063 AN: 18008

Other (OTH) AF: 0.226 AC: 334 AN: 1478

GnomAD4 genome AF: 0.248 AC: 37675 AN: 152104 Hom.: 4733 Cov.: 33 AF XY: 0.245 AC XY: 18232 AN XY: 74366

African (AFR) AF: 0.287 AC: 11924 AN: 41488

American (AMR) AF: 0.230 AC: 3513 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 647 AN: 3470

East Asian (EAS) AF: 0.145 AC: 752 AN: 5182

South Asian (SAS) AF: 0.189 AC: 911 AN: 4816

European-Finnish (FIN) AF: 0.280 AC: 2961 AN: 10574

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16150 AN: 67978

Other (OTH) AF: 0.224 AC: 472 AN: 2108

Alfa AF: 0.263 Hom.: 884

Bravo AF: 0.248

Asia WGS AF: 0.186 AC: 646 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.42
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5030093; hg19: chr3-186461091;