GeneBe

rs4646174

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001371415.1(ACE2):​c.1896+147G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 23)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control

Consequence

ACE2
NM_001371415.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.194

Publications

17 publications found
Variant links:
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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ACE2
NM_001371415.1
MANE Select
c.1896+147G>T
intron
N/ANP_001358344.1Q9BYF1-1
ACE2
NM_021804.3
c.1896+147G>T
intron
N/ANP_068576.1Q9BYF1-1
ACE2
NM_001386259.1
c.1896+147G>T
intron
N/ANP_001373188.1A0A7I2V4H0

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ACE2
ENST00000252519.8
TSL:1 MANE Select
c.1896+147G>T
intron
N/AENSP00000252519.3Q9BYF1-1
ACE2
ENST00000427411.2
TSL:1
c.1896+147G>T
intron
N/AENSP00000389326.1Q9BYF1-1
ENSG00000285602
ENST00000649243.1
n.*1742+2053G>T
intron
N/AENSP00000497489.1A0A3B3IT09

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
420325
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
120707
African (AFR)
AF:
0.00
AC:
0
AN:
11594
American (AMR)
AF:
0.00
AC:
0
AN:
15323
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
10556
East Asian (EAS)
AF:
0.00
AC:
0
AN:
24265
South Asian (SAS)
AF:
0.00
AC:
0
AN:
24902
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
27510
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1562
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
282059
Other (OTH)
AF:
0.00
AC:
0
AN:
22554
GnomAD4 genome
Cov.:
23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
3.6
DANN
Benign
0.43
PhyloP100
0.19

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

Other links and lift over

dbSNP: rs4646174; hg19: chrX-15588271; API