rs4320

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.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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.237

Publications

25 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:

ENSG00000264813 (HGNC:):

ENSG00000264813 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=-0.77).

BP6

Variant 17-63485192-G-A is Benign according to our data. Variant chr17-63485192-G-A is described in ClinVar as Benign. ClinVar VariationId is 1273658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ACE	NM_000789.4 link	c.1922-44G>A		intron_variant	Intron 12 of 24	ENST00000290866.10	NP_000780.1	P12821-1B4DKH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACE	ENST00000290866.10 link	c.1922-44G>A		intron_variant	Intron 12 of 24	1	NM_000789.4	ENSP00000290866.4		P12821-1
ENSG00000264813	ENST00000577647.2 link	n.200-44G>A		intron_variant	Intron 1 of 30	2		ENSP00000464149.1		F6X3S4

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69518

AN:

151814

Hom.:

16191

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.500

AC:

123931

AN:

247918

AF XY:

0.499

show subpopulations

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 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.:

AF XY:

0.479

AC XY:

348108

AN XY:

726358

show subpopulations

African (AFR)

AF:

0.392

AC:

13123

AN:

33474

American (AMR)

AF:

0.573

AC:

25479

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

9722

AN:

26110

East Asian (EAS)

AF:

0.650

AC:

25781

AN:

39676

South Asian (SAS)

AF:

0.579

AC:

49896

AN:

86136

European-Finnish (FIN)

AF:

0.448

AC:

23768

AN:

53100

Middle Eastern (MID)

AF:

0.365

AC:

2101

AN:

5764

European-Non Finnish (NFE)

AF:

0.468

AC:

519892

AN:

1111300

Other (OTH)

AF:

0.469

AC:

28312

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

22062

44125

66187

88250

110312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15648

31296

46944

62592

78240

<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:

0.458

AC:

69581

AN:

151932

Hom.:

16219

Cov.:

AF XY:

0.461

AC XY:

34251

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.400

AC:

16564

AN:

41426

American (AMR)

AF:

0.518

AC:

7916

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

1302

AN:

3468

East Asian (EAS)

AF:

0.667

AC:

3426

AN:

5140

South Asian (SAS)

AF:

0.594

AC:

2855

AN:

4810

European-Finnish (FIN)

AF:

0.449

AC:

4743

AN:

10574

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.462

AC:

31415

AN:

67928

Other (OTH)

AF:

0.422

AC:

889

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1850

3700

5549

7399

9249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.444

Hom.:

6212

Bravo

AF:

0.455

Asia WGS

AF:

0.636

AC:

2210

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 10, 2018

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.4

(source)

DANN

Benign

0.76

PhyloP100

-0.24

PromoterAI

0.0079

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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