rs7853126

Positions:

• chr9-94742975-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.98).
• 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/exons	MANE	UniProt
AOPEP	NM_001193329.3	c.-136+16224A>G		intron_variant		ENST00000375315.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOPEP	ENST00000375315.8	c.-136+16224A>G		intron_variant		1	NM_001193329.3	P1
AOPEP	ENST00000297979.9	c.-136+16224A>G		intron_variant		1
AOPEP	ENST00000277198.6	c.-136+16224A>G		intron_variant		2
AOPEP	ENST00000489318.2	n.148+16224A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.188

Alfa AF: 0.172 Hom.: 602

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7853126; hg19: chr9-97505257;