chrX-15569381-C-G

Variant names:

• chrX-15569381-C-G
• rs4646176
• NM_001371415.1:c.1896+914G>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.1896+914G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 112,031 control chromosomes in the GnomAD database, including 293 homozygotes. There are 1,492 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 0.046 (293 hom., 1492 hem., cov: 23)
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459
• Publications: 24 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACE2	NM_001371415.1	MANE Select	c.1896+914G>C		intron	N/A	NP_001358344.1
	ACE2	NM_021804.3		c.1896+914G>C		intron	N/A	NP_068576.1
	ACE2	NM_001386259.1		c.1896+914G>C		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.1896+914G>C		intron	N/A	ENSP00000252519.3
	ACE2	ENST00000427411.2	TSL:1	c.1896+914G>C		intron	N/A	ENSP00000389326.1
	ENSG00000285602	ENST00000649243.1		n.*1742+2820G>C		intron	N/A	ENSP00000497489.1

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 5202 AN: 111981 Hom.: 293 Cov.: 23

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0313

Gnomad SAS AF: 0.0610

Gnomad FIN AF: 0.000163

Gnomad MID AF: 0.0210

Gnomad NFE AF: 0.000507

Gnomad OTH AF: 0.0432

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

GnomAD4 genome AF: 0.0465 AC: 5206 AN: 112031 Hom.: 293 Cov.: 23 AF XY: 0.0436 AC XY: 1492 AN XY: 34223

African (AFR) AF: 0.151 AC: 4645 AN: 30747

American (AMR) AF: 0.0176 AC: 186 AN: 10581

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.0311 AC: 111 AN: 3568

South Asian (SAS) AF: 0.0620 AC: 166 AN: 2678

European-Finnish (FIN) AF: 0.000163 AC: 1 AN: 6143

Middle Eastern (MID) AF: 0.0230 AC: 5 AN: 217

European-Non Finnish (NFE) AF: 0.000507 AC: 27 AN: 53243

Other (OTH) AF: 0.0427 AC: 65 AN: 1522

Alfa AF: 0.00608 Hom.: 20

Bravo AF: 0.0512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.77
PhyloP100		0.46
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: rs4646176; hg19: chrX-15587504;