rs10514835

chr9-95093361-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The XM_011519121.4(AOPEP):c.2319+12581A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 152,300 control chromosomes in the GnomAD database, including 30 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 0.018 (30 hom., cov: 33)
• Consequence: AOPEP XM_011519121.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0177 (2694/152300) while in subpopulation NFE AF= 0.0248 (1688/68024). AF 95% confidence interval is 0.0238. There are 30 homozygotes in gnomad4. There are 1260 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOPEP	XM_011519121.4	c.2319+12581A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOPEP	ENST00000710812.1	n.410+12581A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2697 AN: 152182 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.00683

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00669

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0177 AC: 2694 AN: 152300 Hom.: 30 Cov.: 33 AF XY: 0.0169 AC XY: 1260 AN XY: 74478

Gnomad4 AFR AF: 0.00683

Gnomad4 AMR AF: 0.0225

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.00669

Gnomad4 NFE AF: 0.0248

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0196 Hom.: 5

Bravo AF: 0.0186

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.13
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10514835; hg19: chr9-97855643;