rs17239917

Variant summary

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

The NM_001150.3(ANPEP):​c.2670-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,290,230 control chromosomes in the GnomAD database, including 19,164 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 0.14 ( 1669 hom., cov: 32)
Exomes 𝑓: 0.17 ( 17495 hom. )

Consequence

ANPEP
NM_001150.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.351

Publications

12 publications found
Variant links:
Genes affected
ANPEP (HGNC:500): (alanyl aminopeptidase, membrane) Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Its function in proximal tubular epithelial cells and other cell types is less clear. The large extracellular carboxyterminal domain contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with known enzymes of this class showed that CD13 and aminopeptidase N are identical. The latter enzyme was thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the CNS. This membrane-bound zinc metalloprotease is known to serve as a receptor for the HCoV-229E alphacoronavirus as well as other non-human coronaviruses. This gene has also been shown to promote angiogenesis, tumor growth, and metastasis and defects in this gene are associated with various types of leukemia and lymphoma. [provided by RefSeq, Apr 2020]

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=-0.81).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANPEPNM_001150.3 linkc.2670-79C>T intron_variant Intron 19 of 20 ENST00000300060.7 NP_001141.2 P15144A0A024RC61Q59E93
ANPEPNM_001381923.1 linkc.2670-79C>T intron_variant Intron 19 of 20 NP_001368852.1
ANPEPNM_001381924.1 linkc.2670-79C>T intron_variant Intron 18 of 19 NP_001368853.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANPEPENST00000300060.7 linkc.2670-79C>T intron_variant Intron 19 of 20 1 NM_001150.3 ENSP00000300060.6 P15144
ANPEPENST00000559874.2 linkc.2670-79C>T intron_variant Intron 19 of 20 3 ENSP00000452934.2 P15144H0YKT6
ANPEPENST00000560137.2 linkc.2670-79C>T intron_variant Intron 19 of 20 3 ENSP00000453413.2 P15144H0YM04
ANPEPENST00000679248.1 linkc.2670-79C>T intron_variant Intron 20 of 21 ENSP00000502886.1 P15144

Frequencies

GnomAD3 genomes
AF:
0.140
AC:
21356
AN:
152074
Hom.:
1670
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0963
Gnomad AMI
AF:
0.0219
Gnomad AMR
AF:
0.110
Gnomad ASJ
AF:
0.194
Gnomad EAS
AF:
0.00154
Gnomad SAS
AF:
0.161
Gnomad FIN
AF:
0.138
Gnomad MID
AF:
0.184
Gnomad NFE
AF:
0.182
Gnomad OTH
AF:
0.164
GnomAD4 exome
AF:
0.168
AC:
190943
AN:
1138038
Hom.:
17495
AF XY:
0.169
AC XY:
97896
AN XY:
577844
show subpopulations
African (AFR)
AF:
0.0992
AC:
2670
AN:
26926
American (AMR)
AF:
0.0826
AC:
3292
AN:
39870
Ashkenazi Jewish (ASJ)
AF:
0.195
AC:
4627
AN:
23676
East Asian (EAS)
AF:
0.000719
AC:
27
AN:
37560
South Asian (SAS)
AF:
0.177
AC:
13675
AN:
77100
European-Finnish (FIN)
AF:
0.139
AC:
7072
AN:
51024
Middle Eastern (MID)
AF:
0.231
AC:
1179
AN:
5110
European-Non Finnish (NFE)
AF:
0.182
AC:
150221
AN:
827056
Other (OTH)
AF:
0.165
AC:
8180
AN:
49716
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
7752
15503
23255
31006
38758
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4628
9256
13884
18512
23140
<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:
0.140
AC:
21354
AN:
152192
Hom.:
1669
Cov.:
32
AF XY:
0.138
AC XY:
10271
AN XY:
74402
show subpopulations
African (AFR)
AF:
0.0962
AC:
3993
AN:
41514
American (AMR)
AF:
0.110
AC:
1679
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.194
AC:
671
AN:
3466
East Asian (EAS)
AF:
0.00154
AC:
8
AN:
5178
South Asian (SAS)
AF:
0.161
AC:
774
AN:
4818
European-Finnish (FIN)
AF:
0.138
AC:
1467
AN:
10612
Middle Eastern (MID)
AF:
0.173
AC:
51
AN:
294
European-Non Finnish (NFE)
AF:
0.182
AC:
12350
AN:
67992
Other (OTH)
AF:
0.162
AC:
341
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
917
1834
2751
3668
4585
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
248
496
744
992
1240
<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:
0.167
Hom.:
7582
Bravo
AF:
0.135
Asia WGS
AF:
0.0730
AC:
254
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
0.89
DANN
Benign
0.75
PhyloP100
-0.35
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

Publications

Other links and lift over

dbSNP: rs17239917; hg19: chr15-90333851; API