3-49682960-C-G

Variant names:

• chr3-49682960-C-G
• rs2960548
• NM_001640.4:c.1986+15C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001640.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APEH	NM_001640.4	MANE Select	c.1986+15C>G		intron	N/A	NP_001631.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APEH	ENST00000296456.10	TSL:1 MANE Select	c.1986+15C>G		intron	N/A	ENSP00000296456.5
	APEH	ENST00000438011.5	TSL:1	c.2001+15C>G		intron	N/A	ENSP00000415862.1
	APEH	ENST00000480772.1	TSL:2	n.239+15C>G		intron	N/A

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

GnomAD2 exomes AF: 0.595 AC: 147184 AN: 247406 AF XY: 0.595

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 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

African (AFR) AF: 0.418 AC: 13988 AN: 33450

American (AMR) AF: 0.745 AC: 33129 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 10749 AN: 26098

East Asian (EAS) AF: 0.953 AC: 37778 AN: 39646

South Asian (SAS) AF: 0.710 AC: 61167 AN: 86112

European-Finnish (FIN) AF: 0.469 AC: 24915 AN: 53126

Middle Eastern (MID) AF: 0.476 AC: 2742 AN: 5764

European-Non Finnish (NFE) AF: 0.530 AC: 588359 AN: 1110694

Other (OTH) AF: 0.544 AC: 32814 AN: 60312

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

African (AFR) AF: 0.428 AC: 17727 AN: 41416

American (AMR) AF: 0.647 AC: 9882 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3470

East Asian (EAS) AF: 0.943 AC: 4852 AN: 5146

South Asian (SAS) AF: 0.728 AC: 3505 AN: 4816

European-Finnish (FIN) AF: 0.462 AC: 4880 AN: 10556

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36180 AN: 67958

Other (OTH) AF: 0.516 AC: 1088 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.97
DANN	Benign	0.62
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2960548; hg19: chr3-49720393;