X-15565781-C-G

Variant names:

• chrX-15565781-C-G
• rs714205
• NM_001371415.1:c.2114+472G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371415.1(ACE2):​c.2114+472G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 111,621 control chromosomes in the GnomAD database, including 1,760 homozygotes. There are 6,645 hemizygotes in GnomAD. 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 0.19 (1760 hom., 6645 hem., cov: 23)
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

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.2114+472G>C		intron	N/A	NP_001358344.1	Q9BYF1-1
	ACE2	NM_021804.3		c.2114+472G>C		intron	N/A	NP_068576.1	Q9BYF1-1
	ACE2	NM_001386259.1		c.2114+472G>C		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.2114+472G>C		intron	N/A	ENSP00000252519.3	Q9BYF1-1
	ACE2	ENST00000427411.2	TSL:1	c.2114+472G>C		intron	N/A	ENSP00000389326.1	Q9BYF1-1
	ENSG00000285602	ENST00000649243.1		n.*1859+472G>C		intron	N/A	ENSP00000497489.1	A0A3B3IT09

Frequencies

GnomAD3 genomes AF: 0.191 AC: 21272 AN: 111566 Hom.: 1759 Cov.: 23

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.173

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.191 AC: 21284 AN: 111621 Hom.: 1760 Cov.: 23 AF XY: 0.197 AC XY: 6645 AN XY: 33815

African (AFR) AF: 0.116 AC: 3570 AN: 30789

American (AMR) AF: 0.337 AC: 3557 AN: 10565

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 411 AN: 2646

East Asian (EAS) AF: 0.526 AC: 1834 AN: 3484

South Asian (SAS) AF: 0.436 AC: 1149 AN: 2634

European-Finnish (FIN) AF: 0.150 AC: 904 AN: 6039

Middle Eastern (MID) AF: 0.176 AC: 38 AN: 216

European-Non Finnish (NFE) AF: 0.177 AC: 9383 AN: 53042

Other (OTH) AF: 0.208 AC: 318 AN: 1526

Alfa AF: 0.186 Hom.: 1234

Bravo AF: 0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.4
DANN	Benign	0.74
PhyloP100		0.28
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: rs714205; hg19: chrX-15583904;