Variant rs4646140 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000252519.8(ACE2):c.802+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,077,075 control chromosomes in the GnomAD database, including 389 homozygotes. There are 3,655 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 0.036 ( 181 hom., 1153 hem., cov: 23)

Exomes 𝑓: 0.0076 ( 208 hom. 2502 hem. )

Consequence

ACE2
ENST00000252519.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

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]

ACE2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACE2	NM_001371415.1 linkuse as main transcript	c.802+24G>A		intron_variant		ENST00000252519.8	NP_001358344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACE2	ENST00000252519.8 linkuse as main transcript	c.802+24G>A		intron_variant		1	NM_001371415.1	ENSP00000252519	P1	Q9BYF1-1

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

4058

AN:

111556

Hom.:

181

Cov.:

AF XY:

0.0341

AC XY:

1152

AN XY:

33756

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0127

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0297

Gnomad SAS

AF:

0.0607

Gnomad FIN

AF:

0.000167

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.000339

Gnomad OTH

AF:

0.0304

GnomAD3 exomes

AF:

0.0180

AC:

2680

AN:

149031

Hom.:

101

AF XY:

0.0166

AC XY:

759

AN XY:

45665

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.00753

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0246

Gnomad SAS exome

AF:

0.0619

Gnomad FIN exome

AF:

0.000395

Gnomad NFE exome

AF:

0.000442

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.00759

AC:

7331

AN:

965468

Hom.:

208

Cov.:

AF XY:

0.00914

AC XY:

2502

AN XY:

273608

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.00912

Gnomad4 ASJ exome

AF:

0.0000577

Gnomad4 EAS exome

AF:

0.0347

Gnomad4 SAS exome

AF:

0.0579

Gnomad4 FIN exome

AF:

0.000254

Gnomad4 NFE exome

AF:

0.000361

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.0363

AC:

4055

AN:

111607

Hom.:

181

Cov.:

AF XY:

0.0341

AC XY:

1153

AN XY:

33817

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0295

Gnomad4 SAS

AF:

0.0613

Gnomad4 FIN

AF:

0.000167

Gnomad4 NFE

AF:

0.000339

Gnomad4 OTH

AF:

0.0301

Alfa

AF:

0.00797

Hom.:

209

Bravo

AF:

0.0400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.1

DANN

Benign

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over