rs6632677

Variant names:

• chrX-15596749-G-C
• rs6632677
• NM_001371415.1:c.187-1746C>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.187-1746C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00586 in 111,878 control chromosomes in the GnomAD database, including 11 homozygotes. There are 210 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 0.0059 (11 hom., 210 hem., cov: 22)
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860
• 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 (EAS) allele frequency at 95% confidence interval = 0.0575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACE2	NM_001371415.1	c.187-1746C>G		intron_variant	Intron 1 of 17	ENST00000252519.8	NP_001358344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACE2	ENST00000252519.8	c.187-1746C>G		intron_variant	Intron 1 of 17	1	NM_001371415.1	ENSP00000252519.3
ENSG00000285602	ENST00000649243.1	n.*265-1746C>G		intron_variant	Intron 6 of 19			ENSP00000497489.1

Frequencies

GnomAD3 genomes AF: 0.00586 AC: 655 AN: 111827 Hom.: 11 Cov.: 22

Gnomad AFR AF: 0.000878

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.00151

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.00557

Gnomad FIN AF: 0.000166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00665

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

GnomAD4 genome AF: 0.00586 AC: 656 AN: 111878 Hom.: 11 Cov.: 22 AF XY: 0.00616 AC XY: 210 AN XY: 34076

African (AFR) AF: 0.000876 AC: 27 AN: 30819

American (AMR) AF: 0.0326 AC: 344 AN: 10549

Ashkenazi Jewish (ASJ) AF: 0.00151 AC: 4 AN: 2647

East Asian (EAS) AF: 0.0643 AC: 228 AN: 3545

South Asian (SAS) AF: 0.00596 AC: 16 AN: 2685

European-Finnish (FIN) AF: 0.000166 AC: 1 AN: 6037

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000470 AC: 25 AN: 53174

Other (OTH) AF: 0.00722 AC: 11 AN: 1523

Alfa AF: 0.00248 Hom.: 7

Bravo AF: 0.00876

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.31
DANN	Benign	0.78
PhyloP100		-0.86
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: rs6632677; hg19: chrX-15614872;