3-49678013-G-A

Position:

• chr3-49678013-G-A

Variant summary

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

The NM_001640.4(APEH):​c.1060+380G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,940 control chromosomes in the GnomAD database, including 21,635 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 0.52 (21635 hom., cov: 32)
• Consequence: APEH NM_001640.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

APEH (HGNC:586): (acylaminoacyl-peptide hydrolase) This gene encodes the enzyme acylpeptide hydrolase, which catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetyl amino acid formed by this hydrolase is further processed to acetate and a free amino acid by an aminoacylase. This gene is located within the same region of chromosome 3 (3p21) as the aminoacylase gene, and deletions at this locus are also associated with a decrease in aminoacylase activity. The acylpeptide hydrolase is a homotetrameric protein of 300 kDa with each subunit consisting of 732 amino acid residues. It can play an important role in destroying oxidatively damaged proteins in living cells. Deletions of this gene locus are found in various types of carcinomas, including small cell lung carcinoma and renal cell carcinoma. [provided by RefSeq, Jul 2008]

APEH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APEH	NM_001640.4	c.1060+380G>A		intron_variant		ENST00000296456.10	NP_001631.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APEH	ENST00000296456.10	c.1060+380G>A		intron_variant		1	NM_001640.4	ENSP00000296456.5

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78436 AN: 151822 Hom.: 21613 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.517 AC: 78492 AN: 151940 Hom.: 21635 Cov.: 32 AF XY: 0.522 AC XY: 38786 AN XY: 74272

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.509

Alfa AF: 0.536 Hom.: 4324

Bravo AF: 0.522

Asia WGS AF: 0.802 AC: 2783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.63

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: rs4855881; hg19: chr3-49715446;