rs266760

Variant names:

• chr3-186743427-G-A
• rs266760
• NM_001102416.3:c.*1096G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-186743427-G-A
• chr3-186743427-G-C

Variant summary

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

The NM_001102416.3(KNG1):​c.*1096G>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 0.256 in 437,306 control chromosomes in the GnomAD database, including 15,407 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 0.29 (7091 hom., cov: 33)
  • Exomes 𝑓: 0.24 (8316 hom.)
• Consequence: KNG1 NM_001102416.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 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.*1096G>A		3_prime_UTR	Exon 10 of 10	NP_001095886.1
	KNG1	NM_000893.4		c.1204-278G>A		intron	N/A	NP_000884.1
	KNG1	NM_001166451.2		c.1096-278G>A		intron	N/A	NP_001159923.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KNG1	ENST00000644859.2	MANE Select	c.*1096G>A		3_prime_UTR	Exon 10 of 10	ENSP00000493985.1
	KNG1	ENST00000287611.8	TSL:1	c.1204-278G>A		intron	N/A	ENSP00000287611.2
	KNG1	ENST00000897802.1		c.*1096G>A		3_prime_UTR	Exon 9 of 9	ENSP00000567861.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44345 AN: 151912 Hom.: 7082 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.236 AC: 67427 AN: 285276 Hom.: 8316 Cov.: 0 AF XY: 0.233 AC XY: 35648 AN XY: 152714

African (AFR) AF: 0.425 AC: 3557 AN: 8364

American (AMR) AF: 0.250 AC: 3349 AN: 13414

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 1769 AN: 8222

East Asian (EAS) AF: 0.133 AC: 2180 AN: 16444

South Asian (SAS) AF: 0.211 AC: 8518 AN: 40462

European-Finnish (FIN) AF: 0.265 AC: 3685 AN: 13894

Middle Eastern (MID) AF: 0.254 AC: 291 AN: 1146

European-Non Finnish (NFE) AF: 0.240 AC: 40163 AN: 167618

Other (OTH) AF: 0.249 AC: 3915 AN: 15712

GnomAD4 genome AF: 0.292 AC: 44379 AN: 152030 Hom.: 7091 Cov.: 33 AF XY: 0.289 AC XY: 21465 AN XY: 74304

African (AFR) AF: 0.422 AC: 17504 AN: 41454

American (AMR) AF: 0.249 AC: 3800 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3472

East Asian (EAS) AF: 0.149 AC: 770 AN: 5172

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4824

European-Finnish (FIN) AF: 0.277 AC: 2921 AN: 10542

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.245 AC: 16627 AN: 67980

Other (OTH) AF: 0.274 AC: 577 AN: 2108

Alfa AF: 0.202 Hom.: 564

Bravo AF: 0.296

Asia WGS AF: 0.207 AC: 719 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.41
DANN	Benign	0.62
PhyloP100		-1.4
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: rs266760; hg19: chr3-186461216;