rs11553742

Variant names:

• chr2-272051-C-T
• rs11553742
• NM_004300.4:c.132C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_004300.4(ACP1):​c.132C>T​(p.Ser44Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0468 in 1,613,538 control chromosomes in the GnomAD database, including 2,083 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.039 (180 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1903 hom.)
• Consequence: ACP1 NM_004300.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07
• Publications: 15 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP7: Synonymous conserved (PhyloP=3.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP1	NM_004300.4	c.132C>T	p.Ser44Ser	synonymous_variant	Exon 3 of 6	ENST00000272065.10	NP_004291.1
ACP1	NM_001040649.3	c.132C>T	p.Ser44Ser	synonymous_variant	Exon 3 of 3		NP_001035739.1
ACP1	NR_024080.2	n.150C>T		non_coding_transcript_exon_variant	Exon 3 of 7
ACP1	NM_007099.4	c.117+112C>T		intron_variant	Intron 2 of 5		NP_009030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP1	ENST00000272065.10	c.132C>T	p.Ser44Ser	synonymous_variant	Exon 3 of 6	1	NM_004300.4	ENSP00000272065.5

Frequencies

GnomAD3 genomes AF: 0.0391 AC: 5930 AN: 151672 Hom.: 180 Cov.: 32

Gnomad AFR AF: 0.00867

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.0957

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0325

GnomAD2 exomes AF: 0.0392 AC: 9844 AN: 251366 AF XY: 0.0398

Gnomad AFR exome AF: 0.00744

Gnomad AMR exome AF: 0.0201

Gnomad ASJ exome AF: 0.0291

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0856

Gnomad NFE exome AF: 0.0571

Gnomad OTH exome AF: 0.0372

GnomAD4 exome AF: 0.0476 AC: 69571 AN: 1461782 Hom.: 1903 Cov.: 42 AF XY: 0.0471 AC XY: 34256 AN XY: 727192

African (AFR) AF: 0.00762 AC: 255 AN: 33480

American (AMR) AF: 0.0211 AC: 943 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0286 AC: 747 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39696

South Asian (SAS) AF: 0.00618 AC: 533 AN: 86256

European-Finnish (FIN) AF: 0.0842 AC: 4499 AN: 53416

Middle Eastern (MID) AF: 0.0205 AC: 118 AN: 5768

European-Non Finnish (NFE) AF: 0.0539 AC: 59947 AN: 1111910

Other (OTH) AF: 0.0418 AC: 2525 AN: 60396

GnomAD4 genome AF: 0.0391 AC: 5930 AN: 151756 Hom.: 180 Cov.: 32 AF XY: 0.0404 AC XY: 2994 AN XY: 74080

African (AFR) AF: 0.00865 AC: 358 AN: 41376

American (AMR) AF: 0.0318 AC: 485 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00748 AC: 36 AN: 4816

European-Finnish (FIN) AF: 0.0957 AC: 997 AN: 10418

Middle Eastern (MID) AF: 0.0379 AC: 11 AN: 290

European-Non Finnish (NFE) AF: 0.0557 AC: 3783 AN: 67956

Other (OTH) AF: 0.0322 AC: 68 AN: 2110

Alfa AF: 0.0484 Hom.: 82

Bravo AF: 0.0336

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.0562

EpiControl AF: 0.0545

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Benign	0.76
PhyloP100		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=85/15	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11553742; hg19: chr2-272051; COSMIC: COSV55245732; COSMIC: COSV55245732;