chr9-94813345-T-A

Position:

• chr9-94813345-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193329.3(AOPEP):​c.1364+12343T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,014 control chromosomes in the GnomAD database, including 35,946 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 0.68 (35946 hom., cov: 31)
• Consequence: AOPEP NM_001193329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOPEP	NM_001193329.3	c.1364+12343T>A		intron_variant		ENST00000375315.8	NP_001180258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AOPEP	ENST00000375315.8	c.1364+12343T>A		intron_variant		1	NM_001193329.3	ENSP00000364464	P1
AOPEP	ENST00000297979.9	c.1364+12343T>A		intron_variant		1		ENSP00000297979
AOPEP	ENST00000277198.6	c.1364+12343T>A		intron_variant		2		ENSP00000277198

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103152 AN: 151896 Hom.: 35902 Cov.: 31

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.679 AC: 103257 AN: 152014 Hom.: 35946 Cov.: 31 AF XY: 0.682 AC XY: 50655 AN XY: 74288

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.645

Alfa AF: 0.624 Hom.: 3779

Bravo AF: 0.689

Asia WGS AF: 0.789 AC: 2744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs391784; hg19: chr9-97575627;