rs11553746

Variant names:

• chr2-272203-C-T
• rs11553746
• ENST00000407983.7:c.284C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040649.3(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 NM_001040649.3 missense
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 5.74
• Publications: 50 publications found

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]

ACMG classification

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: NM_001040649.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP1	NM_004300.4	MANE Select	c.231+53C>T		intron	N/A	NP_004291.1	P24666-1
	ACP1	NM_001040649.3		c.284C>T	p.Thr95Ile	missense	Exon 3 of 3	NP_001035739.1	A0A140VK37
	ACP1	NM_007099.4		c.129C>T	p.Asp43Asp	synonymous	Exon 3 of 6	NP_009030.1	P24666-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP1	ENST00000407983.7	TSL:1	c.284C>T	p.Thr95Ile	missense	Exon 3 of 3	ENSP00000385404.3	P24666-4
	ACP1	ENST00000405233.5	TSL:1	c.158C>T	p.Thr53Ile	missense	Exon 4 of 4	ENSP00000384307.1	F2Z2Q9
	ACP1	ENST00000272067.11	TSL:1	c.129C>T	p.Asp43Asp	synonymous	Exon 3 of 6	ENSP00000272067.6	P24666-2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42417 AN: 151960 Hom.: 6481 Cov.: 32

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

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.: 59 AF XY: 0.333 AC XY: 241899 AN XY: 727160

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

GnomAD4 genome AF: 0.279 AC: 42408 AN: 152078 Hom.: 6477 Cov.: 32 AF XY: 0.280 AC XY: 20834 AN XY: 74326

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: 69 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23532 AN: 67974

Other (OTH) AF: 0.245 AC: 516 AN: 2106

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

Significance: drug response

Revision: no assertion criteria provided

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	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
PhyloP100		5.7
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.14
Sift	Uncertain	0.018	D
Sift4G	Benign	0.17	T
Vest4		0.66
ClinPred		0.046	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=21/79	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11553746; hg19: chr2-272203; COSMIC: COSV55243186; COSMIC: COSV55243186;