chr2-269352-G-A

Variant names:

• chr2-269352-G-A
• rs6755722
• NM_004300.4:c.44-2514G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.93).
• 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 rank	MANE	Protein	UniProt
ACP1	NM_004300.4	c.44-2514G>A		intron_variant	Intron 1 of 5	ENST00000272065.10	NP_004291.1
ACP1	NM_007099.4	c.44-2514G>A		intron_variant	Intron 1 of 5		NP_009030.1
ACP1	NM_001040649.3	c.44-2514G>A		intron_variant	Intron 1 of 2		NP_001035739.1
ACP1	NR_024080.2	n.62-2514G>A		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP1	ENST00000272065.10	c.44-2514G>A		intron_variant	Intron 1 of 5	1	NM_004300.4	ENSP00000272065.5

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

GnomAD2 exomes AF: 0.329 AC: 48007 AN: 145976 AF XY: 0.330

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 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

African (AFR) AF: 0.192 AC: 1649 AN: 8596

American (AMR) AF: 0.244 AC: 6629 AN: 27162

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 3613 AN: 10748

East Asian (EAS) AF: 0.598 AC: 5493 AN: 9180

South Asian (SAS) AF: 0.275 AC: 16396 AN: 59588

European-Finnish (FIN) AF: 0.375 AC: 10143 AN: 27044

Middle Eastern (MID) AF: 0.295 AC: 815 AN: 2766

European-Non Finnish (NFE) AF: 0.344 AC: 54582 AN: 158618

Other (OTH) AF: 0.333 AC: 4758 AN: 14276

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

African (AFR) AF: 0.199 AC: 8244 AN: 41478

American (AMR) AF: 0.268 AC: 4094 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1129 AN: 3462

East Asian (EAS) AF: 0.591 AC: 3057 AN: 5170

South Asian (SAS) AF: 0.272 AC: 1310 AN: 4812

European-Finnish (FIN) AF: 0.399 AC: 4206 AN: 10552

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23288 AN: 67968

Other (OTH) AF: 0.304 AC: 637 AN: 2098

Alfa AF: 0.317 Hom.: 4255

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6755722; hg19: chr2-269352;