X-15601610-C-T

Variant names:

• chrX-15601610-C-T
• rs4646112
• ENST00000427411.2:c.-104+346G>A

Variant summary

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

The ENST00000427411.2(ACE2):​c.-104+346G>A 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 0.018 (39 hom., 441 hem., cov: 20)
• Consequence: ACE2 ENST00000427411.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACE2	NM_021804.3	c.-104+346G>A		intron_variant	Intron 1 of 18		NP_068576.1
ACE2	NM_001389402.1	c.-103-596G>A		intron_variant	Intron 1 of 15		NP_001376331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACE2	ENST00000427411.2	c.-104+346G>A		intron_variant	Intron 1 of 18	1		ENSP00000389326.1
ENSG00000285602	ENST00000649243.1	n.357-596G>A		intron_variant	Intron 5 of 19			ENSP00000497489.1
ACE2	ENST00000678073.1	c.-103-596G>A		intron_variant	Intron 1 of 18			ENSP00000504103.1

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 1889 AN: 107389 Hom.: 39 Cov.: 20

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.00804

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000424

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00855

Gnomad NFE AF: 0.000404

Gnomad OTH AF: 0.0125

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

GnomAD4 genome AF: 0.0176 AC: 1889 AN: 107432 Hom.: 39 Cov.: 20 AF XY: 0.0147 AC XY: 441 AN XY: 29984

African (AFR) AF: 0.0601 AC: 1753 AN: 29145

American (AMR) AF: 0.00726 AC: 73 AN: 10055

Ashkenazi Jewish (ASJ) AF: 0.00804 AC: 21 AN: 2612

East Asian (EAS) AF: 0.00 AC: 0 AN: 3420

South Asian (SAS) AF: 0.000427 AC: 1 AN: 2344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5488

Middle Eastern (MID) AF: 0.00943 AC: 2 AN: 212

European-Non Finnish (NFE) AF: 0.000404 AC: 21 AN: 52028

Other (OTH) AF: 0.0124 AC: 18 AN: 1457

Alfa AF: 0.000291 Hom.: 2

Bravo AF: 0.0215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.47
PhyloP100		-1.3
PromoterAI		0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4646112; hg19: chrX-15619733;