rs4385527

Variant names:

• chr9-94886305-G-A
• rs4385527
• NM_001193329.3:c.1365-37681G>A

Variant summary

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

The NM_001193329.3(AOPEP):​c.1365-37681G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,112 control chromosomes in the GnomAD database, including 8,530 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 0.31 (8530 hom., cov: 32)
• Consequence: AOPEP NM_001193329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOPEP	NM_001193329.3	c.1365-37681G>A		intron_variant	Intron 5 of 16	ENST00000375315.8	NP_001180258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOPEP	ENST00000375315.8	c.1365-37681G>A		intron_variant	Intron 5 of 16	1	NM_001193329.3	ENSP00000364464.2
AOPEP	ENST00000297979.9	c.1365-68872G>A		intron_variant	Intron 5 of 14	1		ENSP00000297979.5
AOPEP	ENST00000277198.6	c.1365-37681G>A		intron_variant	Intron 5 of 7	2		ENSP00000277198.2

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47387 AN: 151994 Hom.: 8529 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.312 AC: 47397 AN: 152112 Hom.: 8530 Cov.: 32 AF XY: 0.309 AC XY: 22940 AN XY: 74338

African (AFR) AF: 0.137 AC: 5695 AN: 41514

American (AMR) AF: 0.305 AC: 4661 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1569 AN: 3460

East Asian (EAS) AF: 0.179 AC: 926 AN: 5180

South Asian (SAS) AF: 0.253 AC: 1217 AN: 4812

European-Finnish (FIN) AF: 0.353 AC: 3733 AN: 10570

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28456 AN: 67972

Other (OTH) AF: 0.347 AC: 734 AN: 2116

Alfa AF: 0.374 Hom.: 20643

Bravo AF: 0.300

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.60
DANN	Benign	0.73
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4385527; hg19: chr9-97648587;