chr9-95085732-G-C

Variant names:

• chr9-95085732-G-C
• rs1011784
• NM_001193329.3:c.*5-950G>C

Variant summary

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

The NM_001193329.3(AOPEP):​c.*5-950G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,132 control chromosomes in the GnomAD database, including 36,192 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 0.69 (36192 hom., cov: 33)
• Consequence: AOPEP NM_001193329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 7 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]

MIR27B (HGNC:31614): (microRNA 27b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOPEP	NM_001193329.3	c.*5-950G>C		intron_variant	Intron 16 of 16	ENST00000375315.8	NP_001180258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOPEP	ENST00000375315.8	c.*5-950G>C		intron_variant	Intron 16 of 16	1	NM_001193329.3	ENSP00000364464.2

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104366 AN: 152012 Hom.: 36182 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.686 AC: 104409 AN: 152132 Hom.: 36192 Cov.: 33 AF XY: 0.687 AC XY: 51068 AN XY: 74350

African (AFR) AF: 0.597 AC: 24761 AN: 41464

American (AMR) AF: 0.721 AC: 11030 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2242 AN: 3472

East Asian (EAS) AF: 0.608 AC: 3136 AN: 5162

South Asian (SAS) AF: 0.637 AC: 3068 AN: 4816

European-Finnish (FIN) AF: 0.766 AC: 8113 AN: 10588

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49707 AN: 68022

Other (OTH) AF: 0.710 AC: 1498 AN: 2110

Alfa AF: 0.706 Hom.: 4724

Bravo AF: 0.677

Asia WGS AF: 0.614 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.50
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1011784; hg19: chr9-97848014;