17-63496400-T-C

Position:

chr17-63496400-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000789.4(ACE):c.3387T>C(p.Phe1129Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,613,968 control chromosomes in the GnomAD database, including 200,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20476 hom., cov: 34)

Exomes 𝑓: 0.49 ( 180509 hom. )

Consequence

ACE
NM_000789.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.87

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 links:

ENSG00000264813 (HGNC:):

ENSG00000264813 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-63496400-T-C is Benign according to our data. Variant chr17-63496400-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 256804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-63496400-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.87 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACE	NM_000789.4 link	c.3387T>C	p.Phe1129Phe	synonymous_variant	23/25	ENST00000290866.10	NP_000780.1	P12821-1B4DKH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACE	ENST00000290866.10 link	c.3387T>C	p.Phe1129Phe	synonymous_variant	23/25	1	NM_000789.4	ENSP00000290866.4		P12821-1
ENSG00000264813	ENST00000577647.2 link	n.1665T>C		non_coding_transcript_exon_variant	12/31	2		ENSP00000464149.1		F6X3S4

Frequencies

GnomAD3 genomes

AF:

0.516

AC:

78371

AN:

152026

Hom.:

20431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.554

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.475

Gnomad OTH

AF:

0.468

GnomAD3 exomes

AF:

0.522

AC:

131102

AN:

251312

Hom.:

35082

AF XY:

0.518

AC XY:

70423

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.587

Gnomad AMR exome

AF:

0.599

Gnomad ASJ exome

AF:

0.372

Gnomad EAS exome

AF:

0.609

Gnomad SAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.475

Gnomad OTH exome

AF:

0.494

GnomAD4 exome

AF:

0.494

AC:

722442

AN:

1461824

Hom.:

180509

Cov.:

AF XY:

0.495

AC XY:

360243

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.576

Gnomad4 AMR exome

AF:

0.593

Gnomad4 ASJ exome

AF:

0.373

Gnomad4 EAS exome

AF:

0.584

Gnomad4 SAS exome

AF:

0.613

Gnomad4 FIN exome

AF:

0.458

Gnomad4 NFE exome

AF:

0.480

Gnomad4 OTH exome

AF:

0.497

GnomAD4 genome

AF:

0.516

AC:

78475

AN:

152144

Hom.:

20476

Cov.:

AF XY:

0.516

AC XY:

38407

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.575

Gnomad4 AMR

AF:

0.555

Gnomad4 ASJ

AF:

0.374

Gnomad4 EAS

AF:

0.603

Gnomad4 SAS

AF:

0.626

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.475

Gnomad4 OTH

AF:

0.474

Alfa

AF:

0.472

Hom.:

31879

Bravo

AF:

0.521

Asia WGS

AF:

0.650

AC:

2260

AN:

3478

EpiCase

AF:

0.465

EpiControl

AF:

0.448

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Renal tubular dysgenesis

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Microvascular complications of diabetes, susceptibility to, 3;C3281105:Hemorrhage, intracerebral, susceptibility to;C5681536:Renal tubular dysgenesis of genetic origin

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.46

DANN

Benign

0.42

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over