chr11-47246999-T-G

Variant summary

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

The NM_001610.4(ACP2):​c.297+642A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,002 control chromosomes in the GnomAD database, including 13,211 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 0.40 ( 13211 hom., cov: 32)

Consequence

ACP2
NM_001610.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.245

Publications

12 publications found
Variant links:
Genes affected
ACP2 (HGNC:123): (acid phosphatase 2, lysosomal) The protein encoded by this gene belongs to the histidine acid phosphatase family, which hydrolyze orthophosphoric monoesters to alcohol and phosphate. This protein is localized to the lysosomal membrane, and is chemically and genetically distinct from the red cell acid phosphatase. Mice lacking this gene showed multiple defects, including bone structure alterations, lysosomal storage defects, and an increased tendency towards seizures. An enzymatically-inactive allele of this gene in mice showed severe growth retardation, hair-follicle abnormalities, and an ataxia-like phenotype. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism. [provided by RefSeq, Oct 2017]
ACP2 Gene-Disease associations (from GenCC):
  • lysosomal acid phosphatase deficiency
    Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

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=-0.89).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACP2NM_001610.4 linkc.297+642A>C intron_variant Intron 3 of 10 ENST00000672073.1 NP_001601.1 P11117-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACP2ENST00000672073.1 linkc.297+642A>C intron_variant Intron 3 of 10 NM_001610.4 ENSP00000500291.1 P11117-1

Frequencies

GnomAD3 genomes
AF:
0.397
AC:
60261
AN:
151884
Hom.:
13201
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.536
Gnomad AMI
AF:
0.133
Gnomad AMR
AF:
0.360
Gnomad ASJ
AF:
0.224
Gnomad EAS
AF:
0.746
Gnomad SAS
AF:
0.466
Gnomad FIN
AF:
0.428
Gnomad MID
AF:
0.263
Gnomad NFE
AF:
0.299
Gnomad OTH
AF:
0.338
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.397
AC:
60302
AN:
152002
Hom.:
13211
Cov.:
32
AF XY:
0.407
AC XY:
30203
AN XY:
74288
show subpopulations
African (AFR)
AF:
0.536
AC:
22203
AN:
41448
American (AMR)
AF:
0.359
AC:
5486
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
0.224
AC:
776
AN:
3464
East Asian (EAS)
AF:
0.746
AC:
3862
AN:
5174
South Asian (SAS)
AF:
0.466
AC:
2244
AN:
4814
European-Finnish (FIN)
AF:
0.428
AC:
4517
AN:
10552
Middle Eastern (MID)
AF:
0.265
AC:
78
AN:
294
European-Non Finnish (NFE)
AF:
0.299
AC:
20310
AN:
67966
Other (OTH)
AF:
0.334
AC:
705
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1764
3529
5293
7058
8822
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
578
1156
1734
2312
2890
<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:
0.411
Hom.:
3142
Bravo
AF:
0.396
Asia WGS
AF:
0.548
AC:
1904
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
2.7
DANN
Benign
0.27
PhyloP100
-0.24
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: rs7129661; hg19: chr11-47268550; API