3-186743088-T-A

Variant names:

• chr3-186743088-T-A
• rs5030091
• NM_001102416.3:c.*757T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001102416.3(KNG1):​c.*757T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KNG1 NM_001102416.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KNG1	NM_001102416.3	MANE Select	c.*757T>A		3_prime_UTR	Exon 10 of 10	NP_001095886.1
	KNG1	NM_000893.4		c.1204-617T>A		intron	N/A	NP_000884.1
	KNG1	NM_001166451.2		c.1096-617T>A		intron	N/A	NP_001159923.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KNG1	ENST00000644859.2	MANE Select	c.*757T>A		3_prime_UTR	Exon 10 of 10	ENSP00000493985.1
	KNG1	ENST00000287611.8	TSL:1	c.1204-617T>A		intron	N/A	ENSP00000287611.2
	KNG1	ENST00000447445.1	TSL:3	c.1096-617T>A		intron	N/A	ENSP00000396025.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 174300 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 83582

African (AFR) AF: 0.00 AC: 0 AN: 3204

American (AMR) AF: 0.00 AC: 0 AN: 254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1116

East Asian (EAS) AF: 0.00 AC: 0 AN: 750

South Asian (SAS) AF: 0.00 AC: 0 AN: 3424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 346

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 159664

Other (OTH) AF: 0.00 AC: 0 AN: 5504

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 18507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.4
DANN	Benign	0.85
PhyloP100		0.34

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: rs5030091; hg19: chr3-186460877;