chr2-276346-T-C

Variant names:

• chr2-276346-T-C
• rs4452185
• NM_004300.4:c.294-634T>C

Variant summary

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

The NM_004300.4(ACP1):​c.294-634T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,144 control chromosomes in the GnomAD database, including 7,566 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 0.30 (7566 hom., cov: 33)
• Consequence: ACP1 NM_004300.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 3 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 (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004300.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP1	NM_004300.4	MANE Select	c.294-634T>C		intron	N/A	NP_004291.1
	ACP1	NM_007099.4		c.294-634T>C		intron	N/A	NP_009030.1
	ACP1	NR_024080.2		n.341-634T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP1	ENST00000272065.10	TSL:1 MANE Select	c.294-634T>C		intron	N/A	ENSP00000272065.5
	ACP1	ENST00000272067.11	TSL:1	c.294-634T>C		intron	N/A	ENSP00000272067.6
	ACP1	ENST00000453390.5	TSL:1	n.*110-634T>C		intron	N/A	ENSP00000411121.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45787 AN: 152026 Hom.: 7572 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.301 AC: 45787 AN: 152144 Hom.: 7566 Cov.: 33 AF XY: 0.304 AC XY: 22594 AN XY: 74358

African (AFR) AF: 0.183 AC: 7593 AN: 41540

American (AMR) AF: 0.269 AC: 4113 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3066 AN: 5174

South Asian (SAS) AF: 0.270 AC: 1298 AN: 4816

European-Finnish (FIN) AF: 0.397 AC: 4195 AN: 10562

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23437 AN: 67982

Other (OTH) AF: 0.300 AC: 634 AN: 2110

Alfa AF: 0.335 Hom.: 3027

Bravo AF: 0.288

Asia WGS AF: 0.369 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.12
DANN	Benign	0.23
PhyloP100		-2.2
Mutation Taster		=100/0	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: rs4452185; hg19: chr2-276346;