chr17-63494091-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.3281+25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 1,612,888 control chromosomes in the GnomAD database, including 1,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 557 hom., cov: 32)

Exomes 𝑓: 0.026 ( 908 hom. )

Consequence

ACE
NM_000789.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.38

Publications

12 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=-0.93).

BP6

Variant 17-63494091-C-T is Benign according to our data. Variant chr17-63494091-C-T is described in ClinVar as Benign. ClinVar VariationId is 1235934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACE	NM_000789.4 link	c.3281+25C>T		intron_variant	Intron 21 of 24	ENST00000290866.10	NP_000780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACE	ENST00000290866.10 link	c.3281+25C>T		intron_variant	Intron 21 of 24	1	NM_000789.4	ENSP00000290866.4
ENSG00000264813	ENST00000577647.2 link	n.1559+25C>T		intron_variant	Intron 10 of 30	2		ENSP00000464149.1

Frequencies

GnomAD3 genomes

AF:

0.0585

AC:

8892

AN:

151972

Hom.:

553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0396

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0232

Gnomad OTH

AF:

0.0565

GnomAD2 exomes

AF:

0.0289

AC:

7231

AN:

249982

AF XY:

0.0277

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.0218

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.00158

Gnomad FIN exome

AF:

0.00995

Gnomad NFE exome

AF:

0.0229

Gnomad OTH exome

AF:

0.0321

GnomAD4 exome

AF:

0.0259

AC:

37847

AN:

1460798

Hom.:

908

Cov.:

AF XY:

0.0257

AC XY:

18703

AN XY:

726682

show subpopulations

African (AFR)

AF:

0.160

AC:

5345

AN:

33470

American (AMR)

AF:

0.0233

AC:

1042

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0188

AC:

491

AN:

26130

East Asian (EAS)

AF:

0.000781

AC:

AN:

39692

South Asian (SAS)

AF:

0.0272

AC:

2341

AN:

86210

European-Finnish (FIN)

AF:

0.0105

AC:

550

AN:

52628

Middle Eastern (MID)

AF:

0.0665

AC:

383

AN:

5760

European-Non Finnish (NFE)

AF:

0.0230

AC:

25576

AN:

1111836

Other (OTH)

AF:

0.0346

AC:

2088

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

2041

4082

6123

8164

10205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1028

2056

3084

4112

5140

<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:

0.0587

AC:

8921

AN:

152090

Hom.:

557

Cov.:

AF XY:

0.0571

AC XY:

4246

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.151

AC:

6253

AN:

41432

American (AMR)

AF:

0.0395

AC:

604

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3470

East Asian (EAS)

AF:

0.00291

AC:

AN:

5160

South Asian (SAS)

AF:

0.0288

AC:

139

AN:

4822

European-Finnish (FIN)

AF:

0.0114

AC:

121

AN:

10594

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0232

AC:

1580

AN:

68012

Other (OTH)

AF:

0.0559

AC:

118

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

393

787

1180

1574

1967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0286

Hom.:

145

Bravo

AF:

0.0645

Asia WGS

AF:

0.0330

AC:

115

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.12

(source)

DANN

Benign

0.70

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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