X-15570148-C-G

Variant names:

• chrX-15570148-C-G
• rs4646174
• NM_001371415.1:c.1896+147G>C

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 17 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=-0.84).

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.1896+147G>C		intron	N/A	NP_001358344.1	Q9BYF1-1
	ACE2	NM_021804.3		c.1896+147G>C		intron	N/A	NP_068576.1	Q9BYF1-1
	ACE2	NM_001386259.1		c.1896+147G>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.1896+147G>C		intron	N/A	ENSP00000252519.3	Q9BYF1-1
	ACE2	ENST00000427411.2	TSL:1	c.1896+147G>C		intron	N/A	ENSP00000389326.1	Q9BYF1-1
	ENSG00000285602	ENST00000649243.1		n.*1742+2053G>C		intron	N/A	ENSP00000497489.1	A0A3B3IT09

Frequencies

GnomAD3 genomes AF: 0.609 AC: 67473 AN: 110831 Hom.: 14808 Cov.: 23

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

African (AFR) AF: 0.449 AC: 5199 AN: 11578

American (AMR) AF: 0.774 AC: 11838 AN: 15303

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 6194 AN: 10548

East Asian (EAS) AF: 0.962 AC: 23348 AN: 24262

South Asian (SAS) AF: 0.710 AC: 17668 AN: 24888

European-Finnish (FIN) AF: 0.715 AC: 19649 AN: 27474

Middle Eastern (MID) AF: 0.564 AC: 879 AN: 1559

European-Non Finnish (NFE) AF: 0.641 AC: 180519 AN: 281556

Other (OTH) AF: 0.644 AC: 14494 AN: 22519

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

African (AFR) AF: 0.451 AC: 13786 AN: 30594

American (AMR) AF: 0.735 AC: 7699 AN: 10469

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 1551 AN: 2632

East Asian (EAS) AF: 0.965 AC: 3381 AN: 3504

South Asian (SAS) AF: 0.715 AC: 1882 AN: 2631

European-Finnish (FIN) AF: 0.705 AC: 4121 AN: 5842

Middle Eastern (MID) AF: 0.556 AC: 119 AN: 214

European-Non Finnish (NFE) AF: 0.637 AC: 33614 AN: 52793

Other (OTH) AF: 0.629 AC: 964 AN: 1532

Alfa AF: 0.589 Hom.: 5029

Bravo AF: 0.611

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.47
PhyloP100		0.19
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: rs4646174; hg19: chrX-15588271; COSMIC: COSV53024786; COSMIC: COSV53024786;