rs233575

Variant names:

• chrX-15564843-G-A
• rs233575
• NM_001371415.1:c.2115-625C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-15564843-G-A
• chrX-15564843-G-C

Variant summary

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

The NM_001371415.1(ACE2):​c.2115-625C>T 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 0.76 (23436 hom., 25194 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 57 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=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACE2	NM_001371415.1	c.2115-625C>T		intron_variant	Intron 16 of 17	ENST00000252519.8	NP_001358344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACE2	ENST00000252519.8	c.2115-625C>T		intron_variant	Intron 16 of 17	1	NM_001371415.1	ENSP00000252519.3
ENSG00000285602	ENST00000649243.1	n.*1860-625C>T		intron_variant	Intron 18 of 19			ENSP00000497489.1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 84371 AN: 110486 Hom.: 23425 Cov.: 22

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.747

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: 0.764 AC: 84443 AN: 110539 Hom.: 23436 Cov.: 22 AF XY: 0.769 AC XY: 25194 AN XY: 32741

African (AFR) AF: 0.951 AC: 28900 AN: 30401

American (AMR) AF: 0.796 AC: 8279 AN: 10401

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1477 AN: 2631

East Asian (EAS) AF: 0.997 AC: 3515 AN: 3525

South Asian (SAS) AF: 0.793 AC: 2057 AN: 2595

European-Finnish (FIN) AF: 0.727 AC: 4206 AN: 5788

Middle Eastern (MID) AF: 0.637 AC: 135 AN: 212

European-Non Finnish (NFE) AF: 0.651 AC: 34355 AN: 52799

Other (OTH) AF: 0.749 AC: 1132 AN: 1511

Alfa AF: 0.675 Hom.: 23614

Bravo AF: 0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.71
DANN	Benign	0.65
PhyloP100		-0.033
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: rs233575; hg19: chrX-15582966; COSMIC: COSV53025110;