rs9822268

Variant names:

• chr3-49682296-G-A
• rs9822268
• NM_001640.4:c.1604-52G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-49682296-G-A
• chr3-49682296-G-C
• chr3-49682296-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001640.4(APEH):​c.1604-52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,514,162 control chromosomes in the GnomAD database, including 65,460 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 0.28 (6464 hom., cov: 34)
  • Exomes 𝑓: 0.29 (58996 hom.)
• Consequence: APEH NM_001640.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 59 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APEH	NM_001640.4	c.1604-52G>A		intron_variant	Intron 17 of 21	ENST00000296456.10	NP_001631.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APEH	ENST00000296456.10	c.1604-52G>A		intron_variant	Intron 17 of 21	1	NM_001640.4	ENSP00000296456.5
APEH	ENST00000438011.5	c.1604-52G>A		intron_variant	Intron 17 of 21	1		ENSP00000415862.1
APEH	ENST00000469362.6	n.*304-52G>A		intron_variant	Intron 6 of 8	3		ENSP00000438180.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42647 AN: 152102 Hom.: 6460 Cov.: 34

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.0454

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.286 AC: 388941 AN: 1361944 Hom.: 58996 Cov.: 25 AF XY: 0.284 AC XY: 193032 AN XY: 678846

African (AFR) AF: 0.274 AC: 8495 AN: 31014

American (AMR) AF: 0.161 AC: 6593 AN: 41068

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 11159 AN: 25282

East Asian (EAS) AF: 0.0428 AC: 1608 AN: 37550

South Asian (SAS) AF: 0.234 AC: 19171 AN: 82006

European-Finnish (FIN) AF: 0.432 AC: 22431 AN: 51906

Middle Eastern (MID) AF: 0.304 AC: 1696 AN: 5584

European-Non Finnish (NFE) AF: 0.292 AC: 301374 AN: 1030712

Other (OTH) AF: 0.289 AC: 16414 AN: 56822

GnomAD4 genome AF: 0.280 AC: 42675 AN: 152218 Hom.: 6464 Cov.: 34 AF XY: 0.282 AC XY: 20993 AN XY: 74406

African (AFR) AF: 0.272 AC: 11293 AN: 41524

American (AMR) AF: 0.208 AC: 3176 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3472

East Asian (EAS) AF: 0.0455 AC: 236 AN: 5186

South Asian (SAS) AF: 0.216 AC: 1043 AN: 4830

European-Finnish (FIN) AF: 0.448 AC: 4743 AN: 10588

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19772 AN: 67998

Other (OTH) AF: 0.286 AC: 605 AN: 2114

Alfa AF: 0.275 Hom.: 16712

Bravo AF: 0.262

Asia WGS AF: 0.135 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.76
PhyloP100		0.093
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)		0.020		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: rs9822268; hg19: chr3-49719729; COSMIC: COSV56532731; COSMIC: COSV56532731;