rs4292

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.-115C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,067,874 control chromosomes in the GnomAD database, including 221,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38380 hom., cov: 32)

Exomes 𝑓: 0.63 ( 183176 hom. )

Consequence

ACE
NM_000789.4 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.577

Publications

34 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 - ACE
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
renal tubular dysgenesis of genetic origin
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, 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=-0.58).

BP6

Variant 17-63476980-C-T is Benign according to our data. Variant chr17-63476980-C-T is described in ClinVar as Benign. ClinVar VariationId is 1285756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000789.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACE	NM_000789.4	MANE Select	c.-115C>T	upstream_gene	N/A	NP_000780.1	P12821-1
ACE	NM_001382700.1		c.-350C>T	upstream_gene	N/A	NP_001369629.1
ACE	NM_001382701.1		c.-729C>T	upstream_gene	N/A	NP_001369630.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACE	ENST00000290866.10	TSL:1 MANE Select	c.-115C>T	upstream_gene	N/A	ENSP00000290866.4	P12821-1
ACE	ENST00000953328.1		c.-115C>T	upstream_gene	N/A	ENSP00000623387.1
ACE	ENST00000884279.1		c.-115C>T	upstream_gene	N/A	ENSP00000554338.1

Frequencies

GnomAD3 genomes

AF:

0.702

AC:

106321

AN:

151430

Hom.:

38316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.882

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.710

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.642

Gnomad SAS

AF:

0.686

Gnomad FIN

AF:

0.614

Gnomad MID

AF:

0.581

Gnomad NFE

AF:

0.621

Gnomad OTH

AF:

0.674

GnomAD4 exome

AF:

0.630

AC:

577373

AN:

916336

Hom.:

183176

AF XY:

0.628

AC XY:

273850

AN XY:

435940

show subpopulations

African (AFR)

AF:

0.893

AC:

16894

AN:

18918

American (AMR)

AF:

0.722

AC:

4975

AN:

6894

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

6343

AN:

11630

East Asian (EAS)

AF:

0.634

AC:

14035

AN:

22140

South Asian (SAS)

AF:

0.675

AC:

12116

AN:

17954

European-Finnish (FIN)

AF:

0.623

AC:

12742

AN:

20450

Middle Eastern (MID)

AF:

0.620

AC:

1546

AN:

2494

European-Non Finnish (NFE)

AF:

0.623

AC:

485037

AN:

779016

Other (OTH)

AF:

0.643

AC:

23685

AN:

36840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

9850

19700

29549

39399

49249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14912

29824

44736

59648

74560

<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:

0.702

AC:

106443

AN:

151538

Hom.:

38380

Cov.:

AF XY:

0.701

AC XY:

51897

AN XY:

74042

show subpopulations

African (AFR)

AF:

0.882

AC:

36546

AN:

41442

American (AMR)

AF:

0.710

AC:

10850

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

1933

AN:

3470

East Asian (EAS)

AF:

0.641

AC:

3244

AN:

5058

South Asian (SAS)

AF:

0.687

AC:

3307

AN:

4812

European-Finnish (FIN)

AF:

0.614

AC:

6447

AN:

10496

Middle Eastern (MID)

AF:

0.572

AC:

166

AN:

290

European-Non Finnish (NFE)

AF:

0.621

AC:

41999

AN:

67672

Other (OTH)

AF:

0.678

AC:

1432

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1566

3132

4699

6265

7831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<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:

0.667

Hom.:

4284

Bravo

AF:

0.715

Asia WGS

AF:

0.703

AC:

2423

AN:

3446

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.58

PromoterAI

0.11

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over