Variant summary

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

The NM_000789.4(ACE):c.2306-105_2306-104insTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as drug response (★★★).


Genomes: not found (cov: 27)


NM_000789.4 intron


Not classified

Clinical Significance

drug response reviewed by expert panel U:1O:1


PhyloP100: -1.31
Variant links:
Genes affected
ACE (HGNC:2707): (angiotensin I converting enzyme) This gene encodes an enzyme involved in blood pressure regulation and electrolyte balance. It catalyzes the conversion of angiotensin I into a physiologically active peptide angiotensin II. Angiotensin II is a potent vasopressor and aldosterone-stimulating peptide that controls blood pressure and fluid-electrolyte balance. This angiotensin converting enzyme (ACE) also inactivates the vasodilator protein, bradykinin. Accordingly, the encoded enzyme increases blood pressure and is a drug target of ACE inhibitors, which are often prescribed to reduce blood pressure. This enzyme additionally plays a role in fertility through its ability to cleave and release GPI-anchored membrane proteins in spermatozoa. Many studies have associated the presence or absence of a 287 bp Alu repeat element in this gene with the levels of circulating enzyme. This polymorphism, as well as mutations in this gene, have been implicated in a wide variety of diseases including cardiovascular pathophysiologies, psoriasis, renal disease, stroke, and Alzheimer's disease. Regulation of the homologous ACE2 gene may be involved in progression of disease caused by several human coronaviruses, including SARS-CoV and SARS-CoV-2. Alternative splicing results in multiple transcript variants encoding both somatic (sACE) and male-specific testicular (tACE) isoforms. [provided by RefSeq, Sep 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.



Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACENM_000789.4 linkuse as main transcriptc.2306-105_2306-104insTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT intron_variant ENST00000290866.10


Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACEENST00000290866.10 linkuse as main transcriptc.2306-105_2306-104insTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT intron_variant 1 NM_000789.4 P1P12821-1


GnomAD3 genomes
GnomAD4 exome
GnomAD4 genome


Significance: drug response
Submissions summary: Uncertain:1Other:1
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

Risk of requirement of invasive mechanical ventilation in patients with severe COVID-19 Uncertain:1
Uncertain significance, no assertion criteria providedresearchHLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas-- -
captopril response - Efficacy Other:1
drug response, reviewed by expert panelcurationPharmGKBMar 24, 2021PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. Drug-variant association: Efficacy

Computational scores

Source: dbNSFP v4.3

Calibrated prediction


Find out detailed SpliceAI scores and Pangolin per-transcript scores at



Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1799752; hg19: chr17-61565890; API