rs3802458

Positions:

• chr9-94978992-A-G

Variant summary

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

The NM_001193329.3(AOPEP):​c.1917-375A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 152,144 control chromosomes in the GnomAD database, including 1,146 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 0.077 (1146 hom., cov: 32)
• Consequence: AOPEP NM_001193329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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]

AOPEP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOPEP	NM_001193329.3	c.1917-375A>G		intron_variant		ENST00000375315.8	NP_001180258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AOPEP	ENST00000375315.8	c.1917-375A>G		intron_variant		1	NM_001193329.3	ENSP00000364464.2

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11736 AN: 152026 Hom.: 1139 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0512

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

GnomAD4 genome AF: 0.0774 AC: 11778 AN: 152144 Hom.: 1146 Cov.: 32 AF XY: 0.0757 AC XY: 5631 AN XY: 74392

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.0331

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0570

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0244 Hom.: 197

Bravo AF: 0.0868

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	-0.98
CADD	Benign	0.015
DANN	Benign	0.21

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: rs3802458; hg19: chr9-97741274;