rs2074192

Variant names:

• chrX-15564667-C-T
• rs2074192
• NM_001371415.1:c.2115-449G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371415.1(ACE2):​c.2115-449G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 110,406 control chromosomes in the GnomAD database, including 6,601 homozygotes. There are 13,020 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 0.40 (6601 hom., 13020 hem., cov: 22)
• Consequence: ACE2 NM_001371415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 120 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACE2	NM_001371415.1	c.2115-449G>A		intron_variant	Intron 16 of 17	ENST00000252519.8	NP_001358344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACE2	ENST00000252519.8	c.2115-449G>A		intron_variant	Intron 16 of 17	1	NM_001371415.1	ENSP00000252519.3
ENSG00000285602	ENST00000649243.1	n.*1860-449G>A		intron_variant	Intron 18 of 19			ENSP00000497489.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 44380 AN: 110362 Hom.: 6601 Cov.: 22

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.402 AC: 44391 AN: 110406 Hom.: 6601 Cov.: 22 AF XY: 0.398 AC XY: 13020 AN XY: 32728

African (AFR) AF: 0.319 AC: 9685 AN: 30382

American (AMR) AF: 0.374 AC: 3878 AN: 10379

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 989 AN: 2633

East Asian (EAS) AF: 0.432 AC: 1509 AN: 3491

South Asian (SAS) AF: 0.255 AC: 671 AN: 2630

European-Finnish (FIN) AF: 0.541 AC: 3104 AN: 5734

Middle Eastern (MID) AF: 0.376 AC: 80 AN: 213

European-Non Finnish (NFE) AF: 0.447 AC: 23606 AN: 52767

Other (OTH) AF: 0.407 AC: 612 AN: 1505

Alfa AF: 0.427 Hom.: 10269

Bravo AF: 0.394

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-0.43
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: rs2074192; hg19: chrX-15582790;