X-15599940-T-C

Variant names:

• chrX-15599940-T-C
• rs1978124
• NM_001371415.1:c.186+786A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001371415.1(ACE2):​c.186+786A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.63 (16733 hom., 20391 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 68 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACE2	NM_001371415.1	c.186+786A>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.186+786A>G		intron_variant	Intron 1 of 17	1	NM_001371415.1	ENSP00000252519.3
ENSG00000285602	ENST00000649243.1	n.*264+786A>G		intron_variant	Intron 6 of 19			ENSP00000497489.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 69238 AN: 109739 Hom.: 16719 Cov.: 22

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.498

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.624

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.631 AC: 69313 AN: 109793 Hom.: 16733 Cov.: 22 AF XY: 0.635 AC XY: 20391 AN XY: 32111

African (AFR) AF: 0.853 AC: 25743 AN: 30171

American (AMR) AF: 0.701 AC: 7201 AN: 10278

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1331 AN: 2618

East Asian (EAS) AF: 0.995 AC: 3461 AN: 3477

South Asian (SAS) AF: 0.732 AC: 1867 AN: 2549

European-Finnish (FIN) AF: 0.531 AC: 3039 AN: 5724

Middle Eastern (MID) AF: 0.521 AC: 110 AN: 211

European-Non Finnish (NFE) AF: 0.480 AC: 25255 AN: 52596

Other (OTH) AF: 0.630 AC: 945 AN: 1501

Alfa AF: 0.409 Hom.: 2554

Bravo AF: 0.661

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.49
PhyloP100		-1.6
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: rs1978124; hg19: chrX-15618063;