rs4385527

chr9-94886305-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.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

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 (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOPEP	NM_001193329.3	c.1365-37681G>A		intron_variant		ENST00000375315.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOPEP	ENST00000375315.8	c.1365-37681G>A		intron_variant		1	NM_001193329.3	P1
AOPEP	ENST00000297979.9	c.1365-68872G>A		intron_variant		1
AOPEP	ENST00000277198.6	c.1365-37681G>A		intron_variant		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

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.347

Alfa AF: 0.395 Hom.: 16835

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

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: rs4385527; hg19: chr9-97648587;