17-63477132-TGCTGCC-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_000789.4(ACE):c.50_55delCGCTGC(p.Pro17_Leu18del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,420,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ACE
NM_000789.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.20

Publications

2 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: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_000789.4

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ACE	NM_000789.4	MANE Select	c.50_55delCGCTGC	p.Pro17_Leu18del	disruptive_inframe_deletion	Exon 1 of 25	NP_000780.1	P12821-1
ACE	NM_001382700.1		c.-186_-181delCGCTGC		5_prime_UTR	Exon 1 of 22	NP_001369629.1
ACE	NM_001382701.1		c.-565_-560delCGCTGC		5_prime_UTR	Exon 1 of 23	NP_001369630.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACE	ENST00000290866.10	TSL:1 MANE Select	c.50_55delCGCTGC	p.Pro17_Leu18del	disruptive_inframe_deletion	Exon 1 of 25	ENSP00000290866.4	P12821-1
ACE	ENST00000953328.1		c.50_55delCGCTGC	p.Pro17_Leu18del	disruptive_inframe_deletion	Exon 1 of 25	ENSP00000623387.1
ACE	ENST00000884279.1		c.50_55delCGCTGC	p.Pro17_Leu18del	disruptive_inframe_deletion	Exon 1 of 25	ENSP00000554338.1

Frequencies

GnomAD3 genomes

AF:

0.0000464

AC:

AN:

150976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000785

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000482

GnomAD2 exomes

AF:

0.0000575

AC:

AN:

69620

AF XY:

0.0000744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000340

Gnomad EAS exome

AF:

0.000389

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.0000362

AC:

AN:

1269426

Hom.:

AF XY:

0.0000480

AC XY:

AN XY:

624926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25636

American (AMR)

AF:

0.00

AC:

AN:

23420

Ashkenazi Jewish (ASJ)

AF:

0.000283

AC:

AN:

21196

East Asian (EAS)

AF:

0.000933

AC:

AN:

26788

South Asian (SAS)

AF:

0.0000151

AC:

AN:

66066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31950

Middle Eastern (MID)

AF:

0.000270

AC:

AN:

3702

European-Non Finnish (NFE)

AF:

0.00000981

AC:

AN:

1018880

Other (OTH)

AF:

0.0000579

AC:

AN:

51788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000463

AC:

AN:

151086

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73854

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41260

American (AMR)

AF:

0.00

AC:

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.000787

AC:

AN:

5084

South Asian (SAS)

AF:

0.000208

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67626

Other (OTH)

AF:

0.000477

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000604

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Microvascular complications of diabetes, susceptibility to, 3;C3281105:Hemorrhage, intracerebral, susceptibility to;C5681536:Renal tubular dysgenesis of genetic origin (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=184/16

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