dbSNP rs1799752: ACE:c.2306-105_2306-104insTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT (chr17-63488529-T-TATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_000789.4(ACE):c.2306-105_2306-104insTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT variant causes a intron change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. Variant has been reported in ClinVar as Uncertain Significance (★★★).

Frequency

Genomes: not found (cov: 27)

Consequence

ACE
NM_000789.4 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -1.31

Publications

295 publications found

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]

ACE Gene-Disease associations (from GenCC):

renal tubular dysgenesis - ACE
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
renal tubular dysgenesis of genetic origin
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia
intracerebral hemorrhage
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACE links:

ENSG00000264813 (HGNC:):

ENSG00000264813 links:

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new If you want to explore the variant's impact on the transcript NM_000789.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 points.

PM2

Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: AR) (threshold 0.001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000789.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACE	NM_000789.4	MANE Select	c.2306-105_2306-104insTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT	intron	N/A	NP_000780.1	P12821-1
ACE	NM_001382700.1		c.1739-105_1739-104insTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT	intron	N/A	NP_001369629.1
ACE	NM_001382701.1		c.1454-105_1454-104insTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT	intron	N/A	NP_001369630.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACE	ENST00000290866.10	TSL:1 MANE Select	c.2306-119_2306-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC	intron	N/A	ENSP00000290866.4	P12821-1
ACE	ENST00000290863.10	TSL:1	c.584-119_584-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC	intron	N/A	ENSP00000290863.6	P12821-3
ENSG00000264813	ENST00000577647.2	TSL:2	n.584-119_584-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC	intron	N/A	ENSP00000464149.1	F6X3S4

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes					27
GnomAD4 exome					13
GnomAD4 genome					27

Showing 3 sources

ClinVar

ClinVar submissions

Significance:drug response

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

Risk of requirement of invasive mechanical ventilation in patients with severe COVID-19 (1)

captopril response - Efficacy (1)

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
PhyloP100	Benign	-	-1.3

Showing 1 of 1 scores

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Publications

Other links and lift over