chr17-63482264-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000789.4(ACE):​c.1119-202A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 151,614 control chromosomes in the GnomAD database, including 39,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 39548 hom., cov: 29)

Consequence

ACE
NM_000789.4 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.0590
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.06).
BP6
Variant 17-63482264-A-G is Benign according to our data. Variant chr17-63482264-A-G is described in ClinVar as [Benign]. Clinvar id is 1260757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACENM_000789.4 linkc.1119-202A>G intron_variant ENST00000290866.10 NP_000780.1 P12821-1B4DKH4
ACENM_001382700.1 linkc.473-123A>G intron_variant NP_001369629.1
ACENM_001382701.1 linkc.267-202A>G intron_variant NP_001369630.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACEENST00000290866.10 linkc.1119-202A>G intron_variant 1 NM_000789.4 ENSP00000290866.4 P12821-1
ACEENST00000428043.5 linkc.1119-202A>G intron_variant 2 ENSP00000397593.2 A0A0A0MSN4
ACEENST00000582678.5 linkn.*518-202A>G intron_variant 2 ENSP00000462995.1 J3KTH9
ACEENST00000584529.5 linkn.1153-202A>G intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.711
AC:
107751
AN:
151496
Hom.:
39478
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.907
Gnomad AMI
AF:
0.572
Gnomad AMR
AF:
0.714
Gnomad ASJ
AF:
0.560
Gnomad EAS
AF:
0.666
Gnomad SAS
AF:
0.687
Gnomad FIN
AF:
0.616
Gnomad MID
AF:
0.582
Gnomad NFE
AF:
0.623
Gnomad OTH
AF:
0.677
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.712
AC:
107885
AN:
151614
Hom.:
39548
Cov.:
29
AF XY:
0.710
AC XY:
52585
AN XY:
74054
show subpopulations
Gnomad4 AFR
AF:
0.908
Gnomad4 AMR
AF:
0.714
Gnomad4 ASJ
AF:
0.560
Gnomad4 EAS
AF:
0.666
Gnomad4 SAS
AF:
0.688
Gnomad4 FIN
AF:
0.616
Gnomad4 NFE
AF:
0.623
Gnomad4 OTH
AF:
0.680
Alfa
AF:
0.706
Hom.:
4981
Bravo
AF:
0.725
Asia WGS
AF:
0.711
AC:
2472
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.1
CADD
Benign
0.50
DANN
Benign
0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4308; hg19: chr17-61559625; API