X-15570148-C-G

Position:

• chrX-15570148-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001371415.1(ACE2):​c.1896+147G>C 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 0.61 (14815 hom., 20551 hem., cov: 23)
  • Exomes 𝑓: 0.67 (66832 hom. 81987 hem.)
  • Failed GnomAD Quality Control
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACE2	NM_001371415.1	c.1896+147G>C		intron_variant		ENST00000252519.8	NP_001358344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACE2	ENST00000252519.8	c.1896+147G>C		intron_variant		1	NM_001371415.1	ENSP00000252519	P1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 67473 AN: 110831 Hom.: 14808 Cov.: 23 AF XY: 0.621 AC XY: 20530 AN XY: 33069

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.543

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.626

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.667 AC: 279788 AN: 419687 Hom.: 66832 AF XY: 0.680 AC XY: 81987 AN XY: 120619

Gnomad4 AFR exome AF: 0.449

Gnomad4 AMR exome AF: 0.774

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.962

Gnomad4 SAS exome AF: 0.710

Gnomad4 FIN exome AF: 0.715

Gnomad4 NFE exome AF: 0.641

Gnomad4 OTH exome AF: 0.644

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.609 AC: 67502 AN: 110886 Hom.: 14815 Cov.: 23 AF XY: 0.620 AC XY: 20551 AN XY: 33134

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.629

Alfa AF: 0.589 Hom.: 5029

Bravo AF: 0.611

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs4646174; hg19: chrX-15588271; COSMIC: COSV53024786; COSMIC: COSV53024786;