Variant rs4646179 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_001371415.1(ACE2):c.2070T>C(p.Asn690=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 1,209,518 control chromosomes in the GnomAD database, including 101 homozygotes. There are 1,221 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 45 hom., 527 hem., cov: 23)

Exomes 𝑓: 0.0023 ( 56 hom. 694 hem. )

Consequence

ACE2
NM_001371415.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0640

Variant links:

Genes affected

ACE2 (HGNC:13557): (angiotensin converting enzyme 2) The protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. ACE2 is known to be expressed in various human organs, and its organ- and cell-specific expression suggests that it may play a role in the regulation of cardiovascular and renal function, as well as fertility. In addition, the encoded protein is a functional receptor for the spike glycoprotein of the human coronavirus HCoV-NL63 and the human severe acute respiratory syndrome coronaviruses, SARS-CoV and SARS-CoV-2, the latter is the causative agent of coronavirus disease-2019 (COVID-19). Multiple splice variants have been found for this gene and the dACE2 (or MIRb-ACE2) splice variant has been found to be interferon inducible. [provided by RefSeq, Nov 2020]

ACE2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-15566297-A-G is Benign according to our data. Variant chrX-15566297-A-G is described in ClinVar as [Benign]. Clinvar id is 778980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.064 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACE2	NM_001371415.1 linkuse as main transcript	c.2070T>C	p.Asn690=	synonymous_variant	16/18	ENST00000252519.8	NP_001358344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACE2	ENST00000252519.8 linkuse as main transcript	c.2070T>C	p.Asn690=	synonymous_variant	16/18	1	NM_001371415.1	ENSP00000252519	P1	Q9BYF1-1

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2026

AN:

111676

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

526

AN XY:

33866

show subpopulations

Gnomad AFR

AF:

0.0617

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00741

Gnomad ASJ

AF:

0.00794

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000375

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00844

Gnomad NFE

AF:

0.000376

Gnomad OTH

AF:

0.0113

GnomAD3 exomes

AF:

0.00561

AC:

1026

AN:

182741

Hom.:

AF XY:

0.00355

AC XY:

239

AN XY:

67285

show subpopulations

Gnomad AFR exome

AF:

0.0649

Gnomad AMR exome

AF:

0.00319

Gnomad ASJ exome

AF:

0.00576

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000158

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000355

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00231

AC:

2535

AN:

1097790

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

694

AN XY:

363200

show subpopulations

Gnomad4 AFR exome

AF:

0.0664

Gnomad4 AMR exome

AF:

0.00369

Gnomad4 ASJ exome

AF:

0.00671

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000296

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000334

Gnomad4 OTH exome

AF:

0.00436

GnomAD4 genome

AF:

0.0181

AC:

2026

AN:

111728

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

527

AN XY:

33928

show subpopulations

Gnomad4 AFR

AF:

0.0615

Gnomad4 AMR

AF:

0.00740

Gnomad4 ASJ

AF:

0.00794

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000376

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000376

Gnomad4 OTH

AF:

0.0111

Alfa

AF:

0.00455

Hom.:

Bravo

AF:

0.0218

EpiCase

AF:

0.000164

EpiControl

AF:

0.000357

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	Labcorp Genetics (formerly Invitae), Labcorp	Jul 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.41

DANN

Benign

0.70

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