Variant chr2-277003-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004300.4(ACP1):c.317A>G(p.Gln106Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,598,632 control chromosomes in the GnomAD database, including 89,383 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 6943 hom., cov: 33)

Exomes 𝑓: 0.33 ( 82440 hom. )

Consequence

ACP1
NM_004300.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.79

Variant links:

Genes affected

ACP1 (HGNC:122): (acid phosphatase 1) The product of this gene belongs to the phosphotyrosine protein phosphatase family of proteins. It functions as an acid phosphatase and a protein tyrosine phosphatase by hydrolyzing protein tyrosine phosphate to protein tyrosine and orthophosphate. This enzyme also hydrolyzes orthophosphoric monoesters to alcohol and orthophosphate. This gene is genetically polymorphic, and three common alleles segregating at the corresponding locus give rise to six phenotypes. Each allele appears to encode at least two electrophoretically different isozymes, Bf and Bs, which are produced in allele-specific ratios. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Aug 2008]

ACP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003926754).

BP6

Variant 2-277003-A-G is Benign according to our data. Variant chr2-277003-A-G is described in ClinVar as [Benign]. Clinvar id is 13685.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACP1	NM_004300.4 linkuse as main transcript	c.317A>G	p.Gln106Arg	missense_variant	5/6	ENST00000272065.10
ACP1	NM_007099.4 linkuse as main transcript	c.317A>G	p.Gln106Arg	missense_variant	5/6
ACP1	NR_024080.2 linkuse as main transcript	n.364A>G		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP1	ENST00000272065.10 linkuse as main transcript	c.317A>G	p.Gln106Arg	missense_variant	5/6	1	NM_004300.4	P3	P24666-1

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44899

AN:

152026

Hom.:

6950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.440

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.310

AC:

76287

AN:

245720

Hom.:

12201

AF XY:

0.314

AC XY:

41674

AN XY:

132876

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.229

Gnomad SAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.366

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.333

AC:

482181

AN:

1446486

Hom.:

82440

Cov.:

AF XY:

0.333

AC XY:

239998

AN XY:

719940

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.249

Gnomad4 ASJ exome

AF:

0.268

Gnomad4 EAS exome

AF:

0.222

Gnomad4 SAS exome

AF:

0.312

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.348

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.295

AC:

44897

AN:

152146

Hom.:

6943

Cov.:

AF XY:

0.296

AC XY:

22035

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.252

Gnomad4 ASJ

AF:

0.271

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.325

Hom.:

9295

Bravo

AF:

0.281

TwinsUK

AF:

0.347

AC:

1287

ALSPAC

AF:

0.336

AC:

1296

ESP6500AA

AF:

0.223

AC:

983

ESP6500EA

AF:

0.344

AC:

2959

ExAC

AF:

0.315

AC:

38242

Asia WGS

AF:

0.270

AC:

939

AN:

3478

EpiCase

AF:

0.334

EpiControl

AF:

0.328

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

ACID PHOSPHATASE 1, SOLUBLE, A/B POLYMORPHISM OF

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Aug 12, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.041

.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.19

N;N

MutationTaster

Benign

0.59

P;P

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.92

N;N

REVEL

Benign

0.27

Sift

Benign

0.18

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.0

B;B

Vest4

0.11

MPC

0.053

ClinPred

0.0041

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.16

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

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