Variant rs4343 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000789.4(ACE):c.2328G>A(p.Thr776=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 148590 control chromosomes in the gnomAD Genomes database, including 24775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24775 hom., cov: 27)

Exomes 𝑓: 0.53 ( 37221 hom. )

Consequence

ACE
NM_000789.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.03

Links

ACE (HGNC:2707):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-63488670-G-A is Benign according to our data. Variant chr17-63488670-G-A is described in ClinVar as [Benign]. Clinvar id is 256803. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-63488670-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.03 with no splicing effect.

BA1

GnomAd highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACE	NM_000789.4 linkuse as main transcript	c.2328G>A	p.Thr776=	synonymous_variant	16/25	ENST00000290866.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACE	ENST00000290866.10 linkuse as main transcript	c.2328G>A	p.Thr776=	synonymous_variant	16/25	1	NM_000789.4	P1	P12821-1

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

83465

AN:

148590

Hom.:

24775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.655

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.406

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.504

GnomAD3 exomes

AF:

0.533

AC:

134087

AN:

251352

Hom.:

37221

AF XY:

0.526

AC XY:

71419

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.760

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.376

Gnomad EAS exome

AF:

0.670

Gnomad SAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.472

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.496

AC:

723840

AN:

1460046

Hom.:

182884

AF XY:

0.496

AC XY:

360156

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.761

Gnomad4 AMR exome

AF:

0.605

Gnomad4 ASJ exome

AF:

0.378

Gnomad4 EAS exome

AF:

0.649

Gnomad4 SAS exome

AF:

0.588

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.476

Gnomad4 OTH exome

AF:

0.508

Alfa

AF:

0.487

Hom.:

38374

Bravo

AF:

0.580

EpiCase

AF:

0.461

EpiControl

AF:

0.445

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 01, 2022	- -

Renotubular dysgenesis

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, PreventionGenetics

- -

Myocardial infarction, susceptibility to

Benign:1

Benign, no assertion criteria provided

reference population

iDNA Genomics

Oct 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

0.40

Dann

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over