rs2960548

chr3-49682960-C-Gchr3-49682960-C-T

Variant summary

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

The NM_001640.4(APEH):c.1986+15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,611,608 control chromosomes in the GnomAD database, including 252,195 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 0.53 (22349 hom., cov: 32)
  • Exomes 𝑓: 0.55 (229846 hom.)
• Consequence: APEH NM_001640.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APEH	NM_001640.4	c.1986+15C>G		intron_variant		ENST00000296456.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APEH	ENST00000296456.10	c.1986+15C>G		intron_variant		1	NM_001640.4	P1
APEH	ENST00000438011.5	c.2001+15C>G		intron_variant		1
APEH	ENST00000480772.1	n.239+15C>G		intron_variant, non_coding_transcript_variant		2
APEH	ENST00000469362.6			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80146 AN: 151834 Hom.: 22329 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.511

GnomAD3 exomes AF: 0.595 AC: 147184 AN: 247406 Hom.: 46613 AF XY: 0.595 AC XY: 79583 AN XY: 133852

Gnomad AFR exome AF: 0.427

Gnomad AMR exome AF: 0.758

Gnomad ASJ exome AF: 0.410

Gnomad EAS exome AF: 0.948

Gnomad SAS exome AF: 0.717

Gnomad FIN exome AF: 0.467

Gnomad NFE exome AF: 0.521

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.552 AC: 805641 AN: 1459656 Hom.: 229846 Cov.: 41 AF XY: 0.556 AC XY: 403788 AN XY: 726046

Gnomad4 AFR exome AF: 0.418

Gnomad4 AMR exome AF: 0.745

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.953

Gnomad4 SAS exome AF: 0.710

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.530

Gnomad4 OTH exome AF: 0.544

GnomAD4 genome AF: 0.528 AC: 80204 AN: 151952 Hom.: 22349 Cov.: 32 AF XY: 0.533 AC XY: 39607 AN XY: 74242

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.516

Alfa AF: 0.443 Hom.: 2289

Bravo AF: 0.535

Asia WGS AF: 0.810 AC: 2809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.97
Dann	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2960548; hg19: chr3-49720393;