rs4320

chr17-63485192-G-Achr17-63485192-G-T

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.1922-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,612,346 control chromosomes in the GnomAD database, including 185,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16219 hom., cov: 31)
  • Exomes 𝑓: 0.48 (168880 hom.)
• Consequence: ACE NM_000789.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.237

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=-0.77).
• BP6: Variant 17-63485192-G-A is Benign according to our data. Variant chr17-63485192-G-A is described in ClinVar as [Benign]. Clinvar id is 1273658.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACE	NM_000789.4	c.1922-44G>A		intron_variant		ENST00000290866.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACE	ENST00000290866.10	c.1922-44G>A		intron_variant		1	NM_000789.4	P1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69518 AN: 151814 Hom.: 16191 Cov.: 31

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.416

GnomAD3 exomes AF: 0.500 AC: 123931 AN: 247918 Hom.: 31836 AF XY: 0.499 AC XY: 66968 AN XY: 134214

Gnomad AFR exome AF: 0.396

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.374

Gnomad EAS exome AF: 0.671

Gnomad SAS exome AF: 0.582

Gnomad FIN exome AF: 0.445

Gnomad NFE exome AF: 0.463

Gnomad OTH exome AF: 0.475

GnomAD4 exome AF: 0.478 AC: 698074 AN: 1460414 Hom.: 168880 Cov.: 46 AF XY: 0.479 AC XY: 348108 AN XY: 726358

Gnomad4 AFR exome AF: 0.392

Gnomad4 AMR exome AF: 0.573

Gnomad4 ASJ exome AF: 0.372

Gnomad4 EAS exome AF: 0.650

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.469

GnomAD4 genome AF: 0.458 AC: 69581 AN: 151932 Hom.: 16219 Cov.: 31 AF XY: 0.461 AC XY: 34251 AN XY: 74258

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.422

Alfa AF: 0.446 Hom.: 2697

Bravo AF: 0.455

Asia WGS AF: 0.636 AC: 2210 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	-0.77
Cadd	Benign	5.4
Dann	Benign	0.76

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: rs4320; hg19: chr17-61562553;