X-15599938-A-G

Variant names:

• chrX-15599938-A-G
• rs2106809
• NM_001371415.1:c.186+788T>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.186+788T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 110,167 control chromosomes in the GnomAD database, including 1,942 homozygotes. There are 6,715 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 0.20 (1942 hom., 6715 hem., cov: 22)
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 137 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 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.186+788T>C		intron	N/A	NP_001358344.1	Q9BYF1-1
	ACE2	NM_021804.3		c.186+788T>C		intron	N/A	NP_068576.1	Q9BYF1-1
	ACE2	NM_001386259.1		c.186+788T>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.186+788T>C		intron	N/A	ENSP00000252519.3	Q9BYF1-1
	ACE2	ENST00000427411.2	TSL:1	c.186+788T>C		intron	N/A	ENSP00000389326.1	Q9BYF1-1
	ENSG00000285602	ENST00000649243.1		n.*264+788T>C		intron	N/A	ENSP00000497489.1	A0A3B3IT09

Frequencies

GnomAD3 genomes AF: 0.202 AC: 22268 AN: 110112 Hom.: 1942 Cov.: 22

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.202 AC: 22278 AN: 110167 Hom.: 1942 Cov.: 22 AF XY: 0.207 AC XY: 6715 AN XY: 32505

African (AFR) AF: 0.116 AC: 3517 AN: 30348

American (AMR) AF: 0.344 AC: 3548 AN: 10300

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 708 AN: 2628

East Asian (EAS) AF: 0.514 AC: 1770 AN: 3446

South Asian (SAS) AF: 0.439 AC: 1118 AN: 2547

European-Finnish (FIN) AF: 0.184 AC: 1071 AN: 5810

Middle Eastern (MID) AF: 0.196 AC: 41 AN: 209

European-Non Finnish (NFE) AF: 0.190 AC: 9993 AN: 52700

Other (OTH) AF: 0.217 AC: 327 AN: 1505

Alfa AF: 0.195 Hom.: 3168

Bravo AF: 0.215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.55
PhyloP100		-0.15
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: rs2106809; hg19: chrX-15618061;