chr1-147654322-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016361.5(ACP6):​c.652C>T​(p.Arg218Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,613,876 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 14 hom., cov: 32)
Exomes 𝑓: 0.015 ( 211 hom. )

Consequence

ACP6
NM_016361.5 missense

Scores

1
6
9

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.39
Variant links:
Genes affected
ACP6 (HGNC:29609): (acid phosphatase 6, lysophosphatidic) This gene encodes a member of the histidine acid phosphatase protein family. The encoded protein hydrolyzes lysophosphatidic acid, which is involved in G protein-coupled receptor signaling, lipid raft modulation, and in balancing lipid composition within the cell. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004639417).
BP6
Variant 1-147654322-G-A is Benign according to our data. Variant chr1-147654322-G-A is described in ClinVar as [Benign]. Clinvar id is 218733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1593/152210) while in subpopulation NFE AF= 0.0172 (1171/68010). AF 95% confidence interval is 0.0164. There are 14 homozygotes in gnomad4. There are 739 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACP6NM_016361.5 linkuse as main transcriptc.652C>T p.Arg218Trp missense_variant 6/10 ENST00000583509.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACP6ENST00000583509.7 linkuse as main transcriptc.652C>T p.Arg218Trp missense_variant 6/101 NM_016361.5 P1Q9NPH0-1

Frequencies

GnomAD3 genomes
AF:
0.0105
AC:
1593
AN:
152092
Hom.:
14
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00287
Gnomad AMI
AF:
0.0428
Gnomad AMR
AF:
0.00760
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00870
Gnomad FIN
AF:
0.00727
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.0172
Gnomad OTH
AF:
0.0100
GnomAD3 exomes
AF:
0.0106
AC:
2671
AN:
251214
Hom.:
24
AF XY:
0.0114
AC XY:
1549
AN XY:
135768
show subpopulations
Gnomad AFR exome
AF:
0.00375
Gnomad AMR exome
AF:
0.00611
Gnomad ASJ exome
AF:
0.000397
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0120
Gnomad FIN exome
AF:
0.00737
Gnomad NFE exome
AF:
0.0158
Gnomad OTH exome
AF:
0.0124
GnomAD4 exome
AF:
0.0153
AC:
22421
AN:
1461666
Hom.:
211
Cov.:
30
AF XY:
0.0153
AC XY:
11145
AN XY:
727170
show subpopulations
Gnomad4 AFR exome
AF:
0.00266
Gnomad4 AMR exome
AF:
0.00682
Gnomad4 ASJ exome
AF:
0.000612
Gnomad4 EAS exome
AF:
0.000378
Gnomad4 SAS exome
AF:
0.0126
Gnomad4 FIN exome
AF:
0.00742
Gnomad4 NFE exome
AF:
0.0177
Gnomad4 OTH exome
AF:
0.0128
GnomAD4 genome
AF:
0.0105
AC:
1593
AN:
152210
Hom.:
14
Cov.:
32
AF XY:
0.00993
AC XY:
739
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.00287
Gnomad4 AMR
AF:
0.00759
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00891
Gnomad4 FIN
AF:
0.00727
Gnomad4 NFE
AF:
0.0172
Gnomad4 OTH
AF:
0.00994
Alfa
AF:
0.0143
Hom.:
36
Bravo
AF:
0.00976
TwinsUK
AF:
0.0224
AC:
83
ALSPAC
AF:
0.0228
AC:
88
ESP6500AA
AF:
0.00318
AC:
14
ESP6500EA
AF:
0.0167
AC:
144
ExAC
AF:
0.0109
AC:
1319
EpiCase
AF:
0.0155
EpiControl
AF:
0.0162

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingGenomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of PhiladelphiaMar 06, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.48
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.085
T;.;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.92
D;D;D
MetaRNN
Benign
0.0046
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
2.9
M;M;.
MutationTaster
Benign
0.57
N;N
PrimateAI
Benign
0.42
T
REVEL
Benign
0.18
Sift4G
Uncertain
0.023
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.15
ClinPred
0.032
T
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.37
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140566115; hg19: chr1-147126437; COSMIC: COSV65076507; COSMIC: COSV65076507; API