rs10821415

Variant names:

• chr9-94951177-C-A
• rs10821415
• NM_001193329.3:c.1662-4000C>A

Variant summary

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

The NM_001193329.3(AOPEP):​c.1662-4000C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,144 control chromosomes in the GnomAD database, including 9,885 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 0.35 (9885 hom., cov: 33)
• Consequence: AOPEP NM_001193329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 59 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOPEP	NM_001193329.3	c.1662-4000C>A		intron_variant	Intron 7 of 16	ENST00000375315.8	NP_001180258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOPEP	ENST00000375315.8	c.1662-4000C>A		intron_variant	Intron 7 of 16	1	NM_001193329.3	ENSP00000364464.2
AOPEP	ENST00000297979.9	c.1365-4000C>A		intron_variant	Intron 5 of 14	1		ENSP00000297979.5
AOPEP	ENST00000462125.5	n.328-4000C>A		intron_variant	Intron 2 of 9	3
AOPEP	ENST00000479161.5	n.384-4000C>A		intron_variant	Intron 3 of 10	5

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52609 AN: 152024 Hom.: 9882 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.346 AC: 52621 AN: 152144 Hom.: 9885 Cov.: 33 AF XY: 0.344 AC XY: 25555 AN XY: 74378

African (AFR) AF: 0.211 AC: 8770 AN: 41532

American (AMR) AF: 0.325 AC: 4972 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1839 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1362 AN: 5176

South Asian (SAS) AF: 0.307 AC: 1482 AN: 4820

European-Finnish (FIN) AF: 0.356 AC: 3769 AN: 10576

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29221 AN: 67972

Other (OTH) AF: 0.371 AC: 783 AN: 2112

Alfa AF: 0.407 Hom.: 33037

Bravo AF: 0.338

Asia WGS AF: 0.269 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.7
DANN	Benign	0.74
PhyloP100		-1.2
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: rs10821415; hg19: chr9-97713459;