rs2158083

Variant names:

• chrX-15590263-C-T
• rs2158083
• NM_001371415.1:c.584-807G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021804.3(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_021804.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 26 publications found

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]

ENSG00000285602 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021804.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACE2	NM_001371415.1	MANE Select	c.584-807G>A		intron	N/A	NP_001358344.1
	ACE2	NM_021804.3		c.584-807G>A		intron	N/A	NP_068576.1
	ACE2	NM_001386259.1		c.584-807G>A		intron	N/A	NP_001373188.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACE2	ENST00000252519.8	TSL:1 MANE Select	c.584-807G>A		intron	N/A	ENSP00000252519.3
	ACE2	ENST00000427411.2	TSL:1	c.584-807G>A		intron	N/A	ENSP00000389326.1
	ENSG00000285602	ENST00000649243.1		n.*662-807G>A		intron	N/A	ENSP00000497489.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 76793 AN: 110063 Hom.: 19223 Cov.: 22

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

African (AFR) AF: 0.783 AC: 23746 AN: 30317

American (AMR) AF: 0.767 AC: 7906 AN: 10308

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1507 AN: 2622

East Asian (EAS) AF: 0.996 AC: 3518 AN: 3533

South Asian (SAS) AF: 0.780 AC: 2025 AN: 2597

European-Finnish (FIN) AF: 0.672 AC: 3877 AN: 5768

Middle Eastern (MID) AF: 0.623 AC: 134 AN: 215

European-Non Finnish (NFE) AF: 0.621 AC: 32672 AN: 52574

Other (OTH) AF: 0.691 AC: 1040 AN: 1505

Alfa AF: 0.661 Hom.: 5321

Bravo AF: 0.714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.66
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2158083; hg19: chrX-15608386;