chr17-63478937-C-G

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.418-70C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 1,362,354 control chromosomes in the GnomAD database, including 265,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 28807 hom., cov: 31)
Exomes 𝑓: 0.62 ( 236312 hom. )

Consequence

ACE
NM_000789.4 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.498

Publications

50 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

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=-0.8).
BP6
Variant 17-63478937-C-G is Benign according to our data. Variant chr17-63478937-C-G is described in ClinVar as Benign. ClinVar VariationId is 1273999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACENM_000789.4 linkc.418-70C>G intron_variant Intron 2 of 24 ENST00000290866.10 NP_000780.1 P12821-1B4DKH4
ACENM_001382700.1 linkc.182+839C>G intron_variant Intron 2 of 21 NP_001369629.1
ACENM_001382701.1 linkc.-198+839C>G intron_variant Intron 2 of 22 NP_001369630.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACEENST00000290866.10 linkc.418-70C>G intron_variant Intron 2 of 24 1 NM_000789.4 ENSP00000290866.4 P12821-1

Frequencies

GnomAD3 genomes
AF:
0.615
AC:
93385
AN:
151798
Hom.:
28773
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.590
Gnomad AMI
AF:
0.573
Gnomad AMR
AF:
0.666
Gnomad ASJ
AF:
0.555
Gnomad EAS
AF:
0.646
Gnomad SAS
AF:
0.625
Gnomad FIN
AF:
0.615
Gnomad MID
AF:
0.541
Gnomad NFE
AF:
0.621
Gnomad OTH
AF:
0.605
GnomAD4 exome
AF:
0.624
AC:
755668
AN:
1210438
Hom.:
236312
Cov.:
17
AF XY:
0.623
AC XY:
379444
AN XY:
609270
show subpopulations
African (AFR)
AF:
0.583
AC:
16194
AN:
27754
American (AMR)
AF:
0.706
AC:
27382
AN:
38778
Ashkenazi Jewish (ASJ)
AF:
0.543
AC:
13073
AN:
24086
East Asian (EAS)
AF:
0.637
AC:
22668
AN:
35600
South Asian (SAS)
AF:
0.626
AC:
48013
AN:
76706
European-Finnish (FIN)
AF:
0.620
AC:
30029
AN:
48422
Middle Eastern (MID)
AF:
0.577
AC:
3067
AN:
5320
European-Non Finnish (NFE)
AF:
0.624
AC:
562926
AN:
901658
Other (OTH)
AF:
0.620
AC:
32316
AN:
52114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
15543
31087
46630
62174
77717
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
14060
28120
42180
56240
70300
<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:
0.615
AC:
93469
AN:
151916
Hom.:
28807
Cov.:
31
AF XY:
0.616
AC XY:
45739
AN XY:
74240
show subpopulations
African (AFR)
AF:
0.590
AC:
24449
AN:
41434
American (AMR)
AF:
0.667
AC:
10186
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.555
AC:
1921
AN:
3464
East Asian (EAS)
AF:
0.646
AC:
3323
AN:
5146
South Asian (SAS)
AF:
0.627
AC:
3004
AN:
4792
European-Finnish (FIN)
AF:
0.615
AC:
6493
AN:
10556
Middle Eastern (MID)
AF:
0.531
AC:
156
AN:
294
European-Non Finnish (NFE)
AF:
0.620
AC:
42148
AN:
67930
Other (OTH)
AF:
0.600
AC:
1266
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1863
3725
5588
7450
9313
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
770
1540
2310
3080
3850
<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:
0.617
Hom.:
3596
Bravo
AF:
0.615
Asia WGS
AF:
0.643
AC:
2235
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
-0.80
CADD
Benign
6.7
DANN
Benign
0.39
PhyloP100
0.50
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs4295; hg19: chr17-61556298; API