rs4646179

chrX-15566297-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0640

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]

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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	UniProt
ACE2	NM_001371415.1	c.2070T>C	p.Asn690=	synonymous_variant	16/18	ENST00000252519.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACE2	ENST00000252519.8	c.2070T>C	p.Asn690=	synonymous_variant	16/18	1	NM_001371415.1	P1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2026 AN: 111676 Hom.: 45 Cov.: 23 AF XY: 0.0155 AC XY: 526 AN XY: 33866

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.: 23 AF XY: 0.00355 AC XY: 239 AN XY: 67285

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.: 56 Cov.: 29 AF XY: 0.00191 AC XY: 694 AN XY: 363200

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.: 45 Cov.: 23 AF XY: 0.0155 AC XY: 527 AN XY: 33928

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.: 98

Bravo AF: 0.0218

EpiCase AF: 0.000164

EpiControl AF: 0.000357

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 30, 2018

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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

Other links and lift over

dbSNP: rs4646179; hg19: chrX-15584420;