Variant chr1-147654322-G-A details in Genebe, Genetics Data Aggregator

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

ACP6 links:

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
ACP6	NM_016361.5 linkuse as main transcript	c.652C>T	p.Arg218Trp	missense_variant	6/10	ENST00000583509.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP6	ENST00000583509.7 linkuse as main transcript	c.652C>T	p.Arg218Trp	missense_variant	6/10	1	NM_016361.5	P1	Q9NPH0-1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1593

AN:

152092

Hom.:

Cov.:

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.:

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.:

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.:

Cov.:

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.:

Bravo

AF:

0.00976

TwinsUK

AF:

0.0224

AC:

ALSPAC

AF:

0.0228

AC:

ESP6500AA

AF:

0.00318

AC:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Mar 06, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.085

T;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.92

D;D;D

MetaRNN

Benign

0.0046

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

M;M;.

MutationTaster

Benign

0.57

N;N

PrimateAI

Benign

0.42

REVEL

Benign

0.18

Sift4G

Uncertain

0.023

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.15

ClinPred

0.032

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over