rs6755722

chr2-269352-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004300.4(ACP1):c.44-2514G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 469,998 control chromosomes in the GnomAD database, including 25,430 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 (7601 hom., cov: 33)
  • Exomes 𝑓: 0.33 (17829 hom.)
• Consequence: ACP1 NM_004300.4 intron
• Scores: Splicing: ADA: 0.00002453
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACP1	NM_004300.4	c.44-2514G>A		intron_variant		ENST00000272065.10
ACP1	NM_001040649.3	c.44-2514G>A		intron_variant
ACP1	NM_007099.4	c.44-2514G>A		intron_variant
ACP1	NR_024080.2	n.62-2514G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP1	ENST00000272065.10	c.44-2514G>A		intron_variant		1	NM_004300.4	P3

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46285 AN: 151902 Hom.: 7603 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.303

GnomAD3 exomes AF: 0.329 AC: 48007 AN: 145976 Hom.: 8465 AF XY: 0.330 AC XY: 25983 AN XY: 78790

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.247

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.597

Gnomad SAS exome AF: 0.275

Gnomad FIN exome AF: 0.375

Gnomad NFE exome AF: 0.341

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.327 AC: 104078 AN: 317978 Hom.: 17829 Cov.: 0 AF XY: 0.325 AC XY: 58467 AN XY: 179720

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.598

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.305 AC: 46300 AN: 152020 Hom.: 7601 Cov.: 33 AF XY: 0.308 AC XY: 22870 AN XY: 74306

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.304

Alfa AF: 0.319 Hom.: 4239

Bravo AF: 0.292

Asia WGS AF: 0.372 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.6
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0040
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: rs6755722; hg19: chr2-269352;