rs2584806

Positions:

• chr9-94766996-C-A
• chr9-94766996-C-G
• chr9-94766996-C-T

Variant summary

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

The NM_001193329.3(AOPEP):​c.798-6006C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 151,828 control chromosomes in the GnomAD database, including 35,816 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 0.68 (35816 hom., cov: 30)
• Consequence: AOPEP NM_001193329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOPEP	NM_001193329.3	c.798-6006C>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.798-6006C>A		intron_variant		1	NM_001193329.3	ENSP00000364464	P1
AOPEP	ENST00000297979.9	c.798-6006C>A		intron_variant		1		ENSP00000297979
AOPEP	ENST00000277198.6	c.798-6006C>A		intron_variant		2		ENSP00000277198
AOPEP	ENST00000489318.2	n.1234-6006C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102887 AN: 151710 Hom.: 35772 Cov.: 30

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.678 AC: 102992 AN: 151828 Hom.: 35816 Cov.: 30 AF XY: 0.681 AC XY: 50557 AN XY: 74202

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.647

Alfa AF: 0.618 Hom.: 4231

Bravo AF: 0.688

Asia WGS AF: 0.791 AC: 2749 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.11

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: rs2584806; hg19: chr9-97529278;