Variant summary

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

The ENST00000407983.7(ACP1):c.284C>T(p.Thr95Ile) variant causes a missense change. The variant allele was found at a frequency of 0.328 in 1,613,824 control chromosomes in the GnomAD database, including 89,201 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.28 ( 6477 hom., cov: 32)

Exomes 𝑓: 0.33 ( 82724 hom. )

Consequence

ACP1
ENST00000407983.7 missense

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 5.74

Publications

50 publications found

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:

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 (MetaRNN=0.0016343594).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000407983.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ACP1	NM_004300.4	MANE Select	c.231+53C>T		intron	N/A	NP_004291.1
ACP1	NM_001040649.3		c.284C>T	p.Thr95Ile	missense	Exon 3 of 3	NP_001035739.1
ACP1	NM_007099.4		c.129C>T	p.Asp43Asp	synonymous	Exon 3 of 6	NP_009030.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ACP1	ENST00000407983.7	TSL:1	c.284C>T	p.Thr95Ile	missense	Exon 3 of 3	ENSP00000385404.3
ACP1	ENST00000405233.5	TSL:1	c.158C>T	p.Thr53Ile	missense	Exon 4 of 4	ENSP00000384307.1
ACP1	ENST00000272067.11	TSL:1	c.129C>T	p.Asp43Asp	synonymous	Exon 3 of 6	ENSP00000272067.6

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42417

AN:

151960

Hom.:

6481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.441

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.248

GnomAD2 exomes

AF:

0.305

AC:

76731

AN:

251206

AF XY:

0.310

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.366

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.333

AC:

486159

AN:

1461746

Hom.:

82724

Cov.:

AF XY:

0.333

AC XY:

241899

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.149

AC:

4984

AN:

33480

American (AMR)

AF:

0.246

AC:

10999

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

7027

AN:

26136

East Asian (EAS)

AF:

0.221

AC:

8785

AN:

39698

South Asian (SAS)

AF:

0.312

AC:

26909

AN:

86256

European-Finnish (FIN)

AF:

0.365

AC:

19480

AN:

53410

Middle Eastern (MID)

AF:

0.253

AC:

1461

AN:

5768

European-Non Finnish (NFE)

AF:

0.349

AC:

387769

AN:

1111918

Other (OTH)

AF:

0.310

AC:

18745

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

22029

44059

66088

88118

110147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12304

24608

36912

49216

61520

<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:

0.279

AC:

42408

AN:

152078

Hom.:

6477

Cov.:

AF XY:

0.280

AC XY:

20834

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.161

AC:

6699

AN:

41500

American (AMR)

AF:

0.248

AC:

3790

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

939

AN:

3466

East Asian (EAS)

AF:

0.235

AC:

1213

AN:

5154

South Asian (SAS)

AF:

0.298

AC:

1434

AN:

4814

European-Finnish (FIN)

AF:

0.361

AC:

3815

AN:

10572

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.346

AC:

23532

AN:

67974

Other (OTH)

AF:

0.245

AC:

516

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1565

3130

4696

6261

7826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.321

Hom.:

16700

Bravo

AF:

0.262

TwinsUK

AF:

0.346

AC:

1284

ALSPAC

AF:

0.336

AC:

1295

ESP6500AA

AF:

0.170

AC:

749

ESP6500EA

AF:

0.345

AC:

2963

ExAC

AF:

0.310

AC:

37609

Asia WGS

AF:

0.266

AC:

925

AN:

3478

EpiCase

AF:

0.333

EpiControl

AF:

0.328

ClinVar

ClinVar submissions as Germline

Significance:drug response

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Thalidomide response (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0046

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

PhyloP100

5.7

PROVEAN

Benign

-0.13

REVEL

Benign

0.14

Sift

Uncertain

0.018

Sift4G

Benign

0.17

Vest4

0.66

ClinPred

0.046

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=21/79

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs11553746

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over