X-15578920-A-T

Variant names:

• chrX-15578920-A-T
• rs4646156
• NM_001371415.1:c.1071-605T>A

Variant summary

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

The NM_001371415.1(ACE2):​c.1071-605T>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 0.69 (19054 hom., 21838 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• Publications: 37 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=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACE2	NM_001371415.1	c.1071-605T>A		intron_variant	Intron 8 of 17	ENST00000252519.8	NP_001358344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACE2	ENST00000252519.8	c.1071-605T>A		intron_variant	Intron 8 of 17	1	NM_001371415.1	ENSP00000252519.3
ENSG00000285602	ENST00000649243.1	n.*1149-605T>A		intron_variant	Intron 13 of 19			ENSP00000497489.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 75642 AN: 108983 Hom.: 19049 Cov.: 22

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.597

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.689

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: 0.694 AC: 75687 AN: 109034 Hom.: 19054 Cov.: 22 AF XY: 0.696 AC XY: 21838 AN XY: 31356

African (AFR) AF: 0.764 AC: 22850 AN: 29902

American (AMR) AF: 0.766 AC: 7806 AN: 10189

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 1626 AN: 2602

East Asian (EAS) AF: 0.996 AC: 3446 AN: 3460

South Asian (SAS) AF: 0.776 AC: 1916 AN: 2468

European-Finnish (FIN) AF: 0.669 AC: 3734 AN: 5582

Middle Eastern (MID) AF: 0.616 AC: 130 AN: 211

European-Non Finnish (NFE) AF: 0.624 AC: 32737 AN: 52461

Other (OTH) AF: 0.692 AC: 1025 AN: 1482

Alfa AF: 0.630 Hom.: 5517

Bravo AF: 0.711

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.65
PhyloP100		-0.51
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: rs4646156; hg19: chrX-15597043;