rs4646181

Variant names:

• chrX-15566066-C-T
• rs4646181
• NM_001371415.1:c.2114+187G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001371415.1(ACE2):​c.2114+187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 112,046 control chromosomes in the GnomAD database, including 2 homozygotes. There are 111 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 0.0040 (2 hom., 111 hem., cov: 23)
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High Homozygotes in GnomAd4 at 2 gene

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+187G>A		intron	N/A	NP_001358344.1	Q9BYF1-1
	ACE2	NM_021804.3		c.2114+187G>A		intron	N/A	NP_068576.1	Q9BYF1-1
	ACE2	NM_001386259.1		c.2114+187G>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.2114+187G>A		intron	N/A	ENSP00000252519.3	Q9BYF1-1
	ACE2	ENST00000427411.2	TSL:1	c.2114+187G>A		intron	N/A	ENSP00000389326.1	Q9BYF1-1
	ENSG00000285602	ENST00000649243.1		n.*1859+187G>A		intron	N/A	ENSP00000497489.1	A0A3B3IT09

Frequencies

GnomAD3 genomes AF: 0.00395 AC: 442 AN: 111994 Hom.: 2 Cov.: 23

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00114

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00263

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

GnomAD4 genome AF: 0.00395 AC: 443 AN: 112046 Hom.: 2 Cov.: 23 AF XY: 0.00324 AC XY: 111 AN XY: 34244

African (AFR) AF: 0.0136 AC: 421 AN: 30871

American (AMR) AF: 0.00113 AC: 12 AN: 10577

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3574

South Asian (SAS) AF: 0.00 AC: 0 AN: 2675

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53174

Other (OTH) AF: 0.00260 AC: 4 AN: 1538

Alfa AF: 0.00756 Hom.: 39

Bravo AF: 0.00467

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.73
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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: rs4646181; hg19: chrX-15584189;