chr17-63479925-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000789.4(ACE):c.655+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,603,872 control chromosomes in the GnomAD database, including 1,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 719 hom., cov: 33)

Exomes 𝑓: 0.0090 ( 827 hom. )

Consequence

ACE
NM_000789.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.152

Publications

5 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 of genetic origin
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
intracerebral hemorrhage
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-63479925-C-T is Benign according to our data. Variant chr17-63479925-C-T is described in ClinVar as Benign. ClinVar VariationId is 256810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ACE	NM_000789.4 link	c.655+13C>T	intron_variant	Intron 4 of 24	ENST00000290866.10	NP_000780.1	P12821-1B4DKH4
ACE	NM_001382700.1 link	c.183-412C>T	intron_variant	Intron 2 of 21		NP_001369629.1
ACE	NM_001382701.1 link	c.-197-412C>T	intron_variant	Intron 2 of 22		NP_001369630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACE	ENST00000290866.10 link	c.655+13C>T		intron_variant	Intron 4 of 24	1	NM_000789.4	ENSP00000290866.4		P12821-1

Frequencies

GnomAD3 genomes

AF:

0.0551

AC:

8382

AN:

152188

Hom.:

711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0592

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0208

AC:

4877

AN:

234696

AF XY:

0.0189

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000283

Gnomad FIN exome

AF:

0.000781

Gnomad NFE exome

AF:

0.000962

Gnomad OTH exome

AF:

0.00894

GnomAD4 exome

AF:

0.00897

AC:

13020

AN:

1451566

Hom.:

827

Cov.:

AF XY:

0.00969

AC XY:

6993

AN XY:

721878

show subpopulations

African (AFR)

AF:

0.190

AC:

6329

AN:

33286

American (AMR)

AF:

0.0122

AC:

538

AN:

44000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25994

East Asian (EAS)

AF:

0.000127

AC:

AN:

39492

South Asian (SAS)

AF:

0.0513

AC:

4385

AN:

85528

European-Finnish (FIN)

AF:

0.000483

AC:

AN:

47592

Middle Eastern (MID)

AF:

0.0173

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.000602

AC:

668

AN:

1109860

Other (OTH)

AF:

0.0162

AC:

974

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

759

1517

2276

3034

3793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0552

AC:

8409

AN:

152306

Hom.:

719

Cov.:

AF XY:

0.0542

AC XY:

4039

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.181

AC:

7529

AN:

41536

American (AMR)

AF:

0.0269

AC:

411

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.0588

AC:

284

AN:

4826

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000911

AC:

AN:

68038

Other (OTH)

AF:

0.0502

AC:

106

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

363

726

1090

1453

1816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0214

Hom.:

Bravo

AF:

0.0625

Asia WGS

AF:

0.0530

AC:

184

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 21, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Renal tubular dysgenesis

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.8

(source)

DANN

Benign

0.72

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over