9-94865485-A-G

Position:

• chr9-94865485-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.1365-58501A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,084 control chromosomes in the GnomAD database, including 14,229 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 0.43 (14229 hom., cov: 32)
• Consequence: AOPEP NM_001193329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.961

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOPEP	NM_001193329.3	c.1365-58501A>G		intron_variant		ENST00000375315.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOPEP	ENST00000375315.8	c.1365-58501A>G		intron_variant		1	NM_001193329.3	P1
AOPEP	ENST00000297979.9	c.1364+64483A>G		intron_variant		1
AOPEP	ENST00000277198.6	c.1365-58501A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64738 AN: 151966 Hom.: 14231 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.426 AC: 64741 AN: 152084 Hom.: 14229 Cov.: 32 AF XY: 0.428 AC XY: 31817 AN XY: 74344

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.437

Alfa AF: 0.455 Hom.: 7541

Bravo AF: 0.421

Asia WGS AF: 0.516 AC: 1794 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.70

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: rs1867102; hg19: chr9-97627767;