Variant rs4320 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000789.4(ACE):c.1922-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,612,346 control chromosomes in the GnomAD database, including 185,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16219 hom., cov: 31)

Exomes 𝑓: 0.48 ( 168880 hom. )

Consequence

ACE
NM_000789.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.237

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 links:

ENSG00000264813 (HGNC:):

ENSG00000264813 links:

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=-0.77).

BP6

Variant 17-63485192-G-A is Benign according to our data. Variant chr17-63485192-G-A is described in ClinVar as [Benign]. Clinvar id is 1273658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACE	NM_000789.4 link	c.1922-44G>A		intron_variant		ENST00000290866.10	NP_000780.1	P12821-1B4DKH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACE	ENST00000290866.10 link	c.1922-44G>A		intron_variant		1	NM_000789.4	ENSP00000290866.4		P12821-1
ENSG00000264813	ENST00000577647.2 link	n.200-44G>A		intron_variant		2		ENSP00000464149.1		F6X3S4

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69518

AN:

151814

Hom.:

16191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.517

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.666

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.500

AC:

123931

AN:

247918

Hom.:

31836

AF XY:

0.499

AC XY:

66968

AN XY:

134214

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.580

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.671

Gnomad SAS exome

AF:

0.582

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.463

Gnomad OTH exome

AF:

0.475

GnomAD4 exome

AF:

0.478

AC:

698074

AN:

1460414

Hom.:

168880

Cov.:

AF XY:

0.479

AC XY:

348108

AN XY:

726358

show subpopulations

Gnomad4 AFR exome

AF:

0.392

Gnomad4 AMR exome

AF:

0.573

Gnomad4 ASJ exome

AF:

0.372

Gnomad4 EAS exome

AF:

0.650

Gnomad4 SAS exome

AF:

0.579

Gnomad4 FIN exome

AF:

0.448

Gnomad4 NFE exome

AF:

0.468

Gnomad4 OTH exome

AF:

0.469

GnomAD4 genome

AF:

0.458

AC:

69581

AN:

151932

Hom.:

16219

Cov.:

AF XY:

0.461

AC XY:

34251

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.400

Gnomad4 AMR

AF:

0.518

Gnomad4 ASJ

AF:

0.375

Gnomad4 EAS

AF:

0.667

Gnomad4 SAS

AF:

0.594

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.462

Gnomad4 OTH

AF:

0.422

Alfa

AF:

0.446

Hom.:

2697

Bravo

AF:

0.455

Asia WGS

AF:

0.636

AC:

2210

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.4

DANN

Benign

0.76

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over