rs2158083

chrX-15590263-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001371415.1(ACE2):c.584-807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (19228 hom., 22789 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BS2: High Homozygotes in GnomAd at 19223 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACE2	NM_001371415.1	c.584-807G>A		intron_variant		ENST00000252519.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACE2	ENST00000252519.8	c.584-807G>A		intron_variant		1	NM_001371415.1	P1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 76793 AN: 110063 Hom.: 19223 Cov.: 22 AF XY: 0.704 AC XY: 22745 AN XY: 32327

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.688

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.698 AC: 76842 AN: 110117 Hom.: 19228 Cov.: 22 AF XY: 0.704 AC XY: 22789 AN XY: 32391

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.691

Alfa AF: 0.661 Hom.: 5321

Bravo AF: 0.714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.19
Dann	Benign	0.66

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: rs2158083; hg19: chrX-15608386;