9-94940218-T-C

Variant names:

• chr9-94940218-T-C
• rs2095069
• NM_001193329.3:c.1661+11687T>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.1661+11687T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,238 control chromosomes in the GnomAD database, including 1,923 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 0.11 (1923 hom., cov: 32)
• Consequence: AOPEP NM_001193329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415
• Publications: 2 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]

ENSG00000224764 (HGNC:58217):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193329.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOPEP	NM_001193329.3	MANE Select	c.1661+11687T>C		intron	N/A	NP_001180258.1
	AOPEP	NM_001386066.1		c.1661+11687T>C		intron	N/A	NP_001372995.1
	AOPEP	NM_001386068.1		c.1661+11687T>C		intron	N/A	NP_001372997.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOPEP	ENST00000375315.8	TSL:1 MANE Select	c.1661+11687T>C		intron	N/A	ENSP00000364464.2
	AOPEP	ENST00000297979.9	TSL:1	c.1365-14959T>C		intron	N/A	ENSP00000297979.5
	AOPEP	ENST00000462125.5	TSL:3	n.328-14959T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16945 AN: 152120 Hom.: 1914 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0333

Gnomad OTH AF: 0.0938

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

GnomAD4 genome AF: 0.112 AC: 16999 AN: 152238 Hom.: 1923 Cov.: 32 AF XY: 0.110 AC XY: 8210 AN XY: 74456

African (AFR) AF: 0.288 AC: 11937 AN: 41506

American (AMR) AF: 0.0966 AC: 1478 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3470

East Asian (EAS) AF: 0.0747 AC: 387 AN: 5178

South Asian (SAS) AF: 0.0926 AC: 447 AN: 4826

European-Finnish (FIN) AF: 0.0174 AC: 185 AN: 10606

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0333 AC: 2267 AN: 68034

Other (OTH) AF: 0.0956 AC: 202 AN: 2112

Alfa AF: 0.0562 Hom.: 2574

Bravo AF: 0.125

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.46
DANN	Benign	0.43
PhyloP100		-0.41
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: rs2095069; hg19: chr9-97702500;