rs3802457

Positions:

• chr9-94979054-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193329.3(AOPEP):​c.1917-313G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 152,126 control chromosomes in the GnomAD database, including 1,182 homozygotes. 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 0.083 (1182 hom., cov: 32)
• Consequence: AOPEP NM_001193329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

Genes affected

AOPEP (HGNC:1361): (aminopeptidase O (putative)) This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

ACMG classification

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 = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOPEP	NM_001193329.3	c.1917-313G>A		intron_variant		ENST00000375315.8	NP_001180258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AOPEP	ENST00000375315.8	c.1917-313G>A		intron_variant		1	NM_001193329.3	ENSP00000364464	P1

Frequencies

GnomAD3 genomes AF: 0.0830 AC: 12612 AN: 152008 Hom.: 1175 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.00453

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0545

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

GnomAD4 genome AF: 0.0832 AC: 12653 AN: 152126 Hom.: 1182 Cov.: 32 AF XY: 0.0808 AC XY: 6014 AN XY: 74392

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.0372

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0574

Gnomad4 FIN AF: 0.00453

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0427 Hom.: 190

Bravo AF: 0.0926

Asia WGS AF: 0.108 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs3802457; hg19: chr9-97741336; COSMIC: COSV52997351;