rs7576247

Positions:

• chr2-277003-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.79

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

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	Protein	UniProt
ACP1	NM_004300.4	c.317A>G	p.Gln106Arg	missense_variant	5/6	ENST00000272065.10	NP_004291.1
ACP1	NM_007099.4	c.317A>G	p.Gln106Arg	missense_variant	5/6		NP_009030.1
ACP1	NR_024080.2	n.364A>G		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACP1	ENST00000272065.10	c.317A>G	p.Gln106Arg	missense_variant	5/6	1	NM_004300.4	ENSP00000272065	P3

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44899 AN: 152026 Hom.: 6950 Cov.: 33

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

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.: 30 AF XY: 0.333 AC XY: 239998 AN XY: 719940

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.: 33 AF XY: 0.296 AC XY: 22035 AN XY: 74366

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

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	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.041	.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.56	T;T
MetaRNN	Benign	0.0039	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.19	N;N
MutationTaster	Benign	0.59	P;P
PrimateAI	Benign	0.42	T
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	T
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

Other links and lift over

dbSNP: rs79716074; hg19: chr2-277003; COSMIC: COSV55243196; COSMIC: COSV55243196;