rs4311

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.1488-58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,530,568 control chromosomes in the GnomAD database, including 235,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28094 hom., cov: 31)

Exomes 𝑓: 0.54 ( 207200 hom. )

Consequence

ACE
NM_000789.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0140

Publications

73 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=-0.89).

BP6

Variant 17-63483402-T-C is Benign according to our data. Variant chr17-63483402-T-C is described in ClinVar as Benign. ClinVar VariationId is 1263928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 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.1488-58T>C	intron	N/A	NP_000780.1	P12821-1
ACE	NM_001382700.1		c.921-58T>C	intron	N/A	NP_001369629.1
ACE	NM_001382701.1		c.636-58T>C	intron	N/A	NP_001369630.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACE	ENST00000290866.10	TSL:1 MANE Select	c.1488-58T>C	intron	N/A	ENSP00000290866.4	P12821-1
ACE	ENST00000953328.1		c.1488-58T>C	intron	N/A	ENSP00000623387.1
ACE	ENST00000884279.1		c.1488-58T>C	intron	N/A	ENSP00000554338.1

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

91078

AN:

151870

Hom.:

28035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.663

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.547

GnomAD4 exome

AF:

0.545

AC:

750923

AN:

1378580

Hom.:

207200

Cov.:

AF XY:

0.545

AC XY:

376323

AN XY:

690722

show subpopulations

African (AFR)

AF:

0.755

AC:

23929

AN:

31690

American (AMR)

AF:

0.622

AC:

27729

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

11138

AN:

25584

East Asian (EAS)

AF:

0.652

AC:

25611

AN:

39294

South Asian (SAS)

AF:

0.640

AC:

54161

AN:

84674

European-Finnish (FIN)

AF:

0.535

AC:

28466

AN:

53198

Middle Eastern (MID)

AF:

0.461

AC:

2593

AN:

5630

European-Non Finnish (NFE)

AF:

0.527

AC:

545678

AN:

1036384

Other (OTH)

AF:

0.550

AC:

31618

AN:

57528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

19507

39014

58521

78028

97535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15370

30740

46110

61480

76850

<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:

0.600

AC:

91201

AN:

151988

Hom.:

28094

Cov.:

AF XY:

0.601

AC XY:

44656

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.751

AC:

31130

AN:

41432

American (AMR)

AF:

0.592

AC:

9049

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

1548

AN:

3470

East Asian (EAS)

AF:

0.663

AC:

3424

AN:

5164

South Asian (SAS)

AF:

0.650

AC:

3129

AN:

4812

European-Finnish (FIN)

AF:

0.535

AC:

5649

AN:

10552

Middle Eastern (MID)

AF:

0.418

AC:

122

AN:

292

European-Non Finnish (NFE)

AF:

0.523

AC:

35519

AN:

67972

Other (OTH)

AF:

0.551

AC:

1161

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1819

3638

5457

7276

9095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.545

Hom.:

66153

Bravo

AF:

0.608

Asia WGS

AF:

0.692

AC:

2404

AN:

3478

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

-0.89

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

-0.014

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over