rs869320718

Positions:

• chr3-186740983-TTTGTTGTTGTTGTTGTTTGTTTTTTGT-TGGTGGTGGTGGTGGTGGTTTGTTTTTGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001102416.3(KNG1):​c.1126-538_1126-512delTTGTTGTTGTTGTTGTTTGTTTTTTGTinsGGTGGTGGTGGTGGTGGTTTGTTTTTGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Affects (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: KNG1 NM_001102416.3 intron
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 0.226

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KNG1	NM_001102416.3	c.1126-538_1126-512delTTGTTGTTGTTGTTGTTTGTTTTTTGTinsGGTGGTGGTGGTGGTGGTTTGTTTTTGG		intron_variant		ENST00000644859.2	NP_001095886.1
KNG1	NM_000893.4	c.1126-538_1126-512delTTGTTGTTGTTGTTGTTTGTTTTTTGTinsGGTGGTGGTGGTGGTGGTTTGTTTTTGG		intron_variant			NP_000884.1
KNG1	NM_001166451.2	c.1018-538_1018-512delTTGTTGTTGTTGTTGTTTGTTTTTTGTinsGGTGGTGGTGGTGGTGGTTTGTTTTTGG		intron_variant			NP_001159923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KNG1	ENST00000644859.2	c.1126-538_1126-512delTTGTTGTTGTTGTTGTTTGTTTTTTGTinsGGTGGTGGTGGTGGTGGTTTGTTTTTGG		intron_variant			NM_001102416.3	ENSP00000493985.1

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

High molecular weight kininogen deficiency Other:1

Affects, no assertion criteria provided

literature only

OMIM

Jun 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs869320718; hg19: chr3-186458773;