rs7853126

Variant names:

• chr9-94742975-A-G
• rs7853126
• NM_001193329.3:c.-136+16224A>G

Variant summary

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

The NM_001193329.3(AOPEP):​c.-136+16224A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,868 control chromosomes in the GnomAD database, including 5,590 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 0.23 (5590 hom., cov: 31)
• Consequence: AOPEP NM_001193329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOPEP	NM_001193329.3	c.-136+16224A>G		intron_variant	Intron 1 of 16	ENST00000375315.8	NP_001180258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOPEP	ENST00000375315.8	c.-136+16224A>G		intron_variant	Intron 1 of 16	1	NM_001193329.3	ENSP00000364464.2
AOPEP	ENST00000297979.9	c.-136+16224A>G		intron_variant	Intron 1 of 14	1		ENSP00000297979.5
AOPEP	ENST00000277198.6	c.-136+16224A>G		intron_variant	Intron 1 of 7	2		ENSP00000277198.2
AOPEP	ENST00000489318.2	n.148+16224A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34086 AN: 151750 Hom.: 5558 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.225 AC: 34182 AN: 151868 Hom.: 5590 Cov.: 31 AF XY: 0.225 AC XY: 16726 AN XY: 74242

African (AFR) AF: 0.456 AC: 18860 AN: 41354

American (AMR) AF: 0.217 AC: 3301 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3470

East Asian (EAS) AF: 0.152 AC: 783 AN: 5168

South Asian (SAS) AF: 0.204 AC: 980 AN: 4808

European-Finnish (FIN) AF: 0.158 AC: 1675 AN: 10568

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.113 AC: 7708 AN: 67958

Other (OTH) AF: 0.188 AC: 397 AN: 2110

Alfa AF: 0.179 Hom.: 674

Bravo AF: 0.238

Asia WGS AF: 0.207 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.59
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7853126; hg19: chr9-97505257;