NM_001371415.1:c.1897-1015G>A

Variant names:

• chrX-15568841-C-T
• rs4240157
• NM_001371415.1:c.1897-1015G>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.1897-1015G>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 0.61 (14627 hom., 19475 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 76 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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371415.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACE2	NM_001371415.1	MANE Select	c.1897-1015G>A		intron	N/A	NP_001358344.1	Q9BYF1-1
	ACE2	NM_021804.3		c.1897-1015G>A		intron	N/A	NP_068576.1	Q9BYF1-1
	ACE2	NM_001386259.1		c.1897-1015G>A		intron	N/A	NP_001373188.1	A0A7I2V4H0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACE2	ENST00000252519.8	TSL:1 MANE Select	c.1897-1015G>A		intron	N/A	ENSP00000252519.3	Q9BYF1-1
	ACE2	ENST00000427411.2	TSL:1	c.1897-1015G>A		intron	N/A	ENSP00000389326.1	Q9BYF1-1
	ENSG00000285602	ENST00000649243.1		n.*1743-2472G>A		intron	N/A	ENSP00000497489.1	A0A3B3IT09

Frequencies

GnomAD3 genomes AF: 0.605 AC: 66104 AN: 109219 Hom.: 14619 Cov.: 22

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.623

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: 0.605 AC: 66132 AN: 109269 Hom.: 14627 Cov.: 22 AF XY: 0.615 AC XY: 19475 AN XY: 31645

African (AFR) AF: 0.451 AC: 13558 AN: 30060

American (AMR) AF: 0.730 AC: 7438 AN: 10186

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1423 AN: 2626

East Asian (EAS) AF: 0.966 AC: 3319 AN: 3436

South Asian (SAS) AF: 0.716 AC: 1798 AN: 2512

European-Finnish (FIN) AF: 0.686 AC: 3821 AN: 5568

Middle Eastern (MID) AF: 0.571 AC: 121 AN: 212

European-Non Finnish (NFE) AF: 0.635 AC: 33353 AN: 52530

Other (OTH) AF: 0.626 AC: 926 AN: 1479

Alfa AF: 0.623 Hom.: 89724

Bravo AF: 0.610

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.062
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4240157; hg19: chrX-15586964;