chrX-15601610-C-T

Position:

• chrX-15601610-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ACE2	NM_001389402.1	c.-103-596G>A		intron_variant
ACE2	NM_021804.3	c.-104+346G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACE2	ENST00000427411.2	c.-104+346G>A		intron_variant		1		P1
ACE2	ENST00000678073.1	c.-103-596G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 1889 AN: 107389 Hom.: 39 Cov.: 20 AF XY: 0.0147 AC XY: 440 AN XY: 29929

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

Gnomad4 AFR AF: 0.0601

Gnomad4 AMR AF: 0.00726

Gnomad4 ASJ AF: 0.00804

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000427

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000404

Gnomad4 OTH AF: 0.0124

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4646112; hg19: chrX-15619733;