rs4344

chr17-63489363-G-Achr17-63489363-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000789.4(ACE):c.2641+231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,042 control chromosomes in the GnomAD database, including 16,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (16463 hom., cov: 32)
• Consequence: ACE NM_000789.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.187

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-63489363-G-A is Benign according to our data. Variant chr17-63489363-G-A is described in ClinVar as [Benign]. Clinvar id is 1226144.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACE	NM_000789.4	c.2641+231G>A		intron_variant		ENST00000290866.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACE	ENST00000290866.10	c.2641+231G>A		intron_variant		1	NM_000789.4	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70098 AN: 151924 Hom.: 16433 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.461 AC: 70166 AN: 152042 Hom.: 16463 Cov.: 32 AF XY: 0.464 AC XY: 34507 AN XY: 74328

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.427

Alfa AF: 0.444 Hom.: 14498

Bravo AF: 0.459

Asia WGS AF: 0.635 AC: 2209 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.1
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs4344; hg19: chr17-61566724;