17-63498093-ACT-ACTCT

Position:

• chr17-63498093-ACT-ACTCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000789.4(ACE):​c.*730_*731dupCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (20935 hom., cov: 0)
  • Exomes 𝑓: 0.41 (237 hom.)
• Consequence: ACE NM_000789.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.813

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]

ENSG00000264813 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-63498093-A-ACT is Benign according to our data. Variant chr17-63498093-A-ACT is described in ClinVar as [Benign]. Clinvar id is 324435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACE	NM_000789.4	c.*730_*731dupCT		3_prime_UTR_variant	25/25	ENST00000290866.10	NP_000780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACE	ENST00000290866.10	c.*730_*731dupCT		3_prime_UTR_variant	25/25	1	NM_000789.4	ENSP00000290866.4
ENSG00000264813	ENST00000577647.2	n.1969+1111_1969+1112dupCT		intron_variant		2		ENSP00000464149.1
ACE	ENST00000428043.5	c.*1073_*1074dupCT		3_prime_UTR_variant	24/24	2		ENSP00000397593.2

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79162 AN: 151808 Hom.: 20880 Cov.: 0

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.407 AC: 951 AN: 2334 Hom.: 237 Cov.: 0 AF XY: 0.412 AC XY: 480 AN XY: 1164

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.467

GnomAD4 genome AF: 0.522 AC: 79281 AN: 151926 Hom.: 20935 Cov.: 0 AF XY: 0.523 AC XY: 38842 AN XY: 74242

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.483

Bravo AF: 0.523

Asia WGS AF: 0.663 AC: 2304 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Renal tubular dysgenesis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs4366; hg19: chr17-61575454;