rs1514282

Variant names:

• chrX-15564640-T-C
• rs1514282
• NM_001371415.1:c.2115-422A>G

Variant summary

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

The NM_001371415.1(ACE2):​c.2115-422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 111,792 control chromosomes in the GnomAD database, including 1,053 homozygotes. There are 2,845 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 0.091 (1053 hom., 2845 hem., cov: 23)
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 11 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACE2	NM_001371415.1	c.2115-422A>G		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.2115-422A>G		intron_variant	Intron 16 of 17	1	NM_001371415.1	ENSP00000252519.3
ENSG00000285602	ENST00000649243.1	n.*1860-422A>G		intron_variant	Intron 18 of 19			ENSP00000497489.1

Frequencies

GnomAD3 genomes AF: 0.0908 AC: 10146 AN: 111742 Hom.: 1052 Cov.: 23

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0345

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0311

Gnomad SAS AF: 0.0630

Gnomad FIN AF: 0.000163

Gnomad MID AF: 0.0462

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0911 AC: 10179 AN: 111792 Hom.: 1053 Cov.: 23 AF XY: 0.0836 AC XY: 2845 AN XY: 34018

African (AFR) AF: 0.307 AC: 9346 AN: 30486

American (AMR) AF: 0.0345 AC: 364 AN: 10566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.0309 AC: 111 AN: 3587

South Asian (SAS) AF: 0.0640 AC: 172 AN: 2689

European-Finnish (FIN) AF: 0.000163 AC: 1 AN: 6132

Middle Eastern (MID) AF: 0.0509 AC: 11 AN: 216

European-Non Finnish (NFE) AF: 0.00113 AC: 60 AN: 53241

Other (OTH) AF: 0.0740 AC: 114 AN: 1541

Alfa AF: 0.0715 Hom.: 328

Bravo AF: 0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.2
DANN	Benign	0.52
PhyloP100		-0.0030
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: rs1514282; hg19: chrX-15582763;