rs9822268

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0930

Publications

59 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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
APEHNM_001640.4 linkc.1604-52G>A intron_variant Intron 17 of 21 ENST00000296456.10 NP_001631.3 P13798

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APEHENST00000296456.10 linkc.1604-52G>A intron_variant Intron 17 of 21 1 NM_001640.4 ENSP00000296456.5 P13798
APEHENST00000438011.5 linkc.1604-52G>A intron_variant Intron 17 of 21 1 ENSP00000415862.1 C9JIF9
APEHENST00000469362.6 linkn.*304-52G>A intron_variant Intron 6 of 8 3 ENSP00000438180.1 H0YFE5

Frequencies

GnomAD3 genomes
AF:
0.280
AC:
42647
AN:
152102
Hom.:
6460
Cov.:
34
show subpopulations
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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
14253
28507
42760
57014
71267
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
9642
19284
28926
38568
48210
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.280
AC:
42675
AN:
152218
Hom.:
6464
Cov.:
34
AF XY:
0.282
AC XY:
20993
AN XY:
74406
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1636
3272
4907
6543
8179
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
434
868
1302
1736
2170
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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

Publications

Other links and lift over

dbSNP: rs9822268; hg19: chr3-49719729; COSMIC: COSV56532731; COSMIC: COSV56532731; API