rs11039146

Positions:

• chr11-47245211-G-A

Variant summary

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

The NM_001610.4(ACP2):​c.639+94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 1,345,378 control chromosomes in the GnomAD database, including 1,494 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 0.034 (124 hom., cov: 33)
  • Exomes 𝑓: 0.041 (1370 hom.)
• Consequence: ACP2 NM_001610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

Genes affected

ACP2 (HGNC:123): (acid phosphatase 2, lysosomal) The protein encoded by this gene belongs to the histidine acid phosphatase family, which hydrolyze orthophosphoric monoesters to alcohol and phosphate. This protein is localized to the lysosomal membrane, and is chemically and genetically distinct from the red cell acid phosphatase. Mice lacking this gene showed multiple defects, including bone structure alterations, lysosomal storage defects, and an increased tendency towards seizures. An enzymatically-inactive allele of this gene in mice showed severe growth retardation, hair-follicle abnormalities, and an ataxia-like phenotype. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism. [provided by RefSeq, Oct 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACP2	NM_001610.4	c.639+94C>T		intron_variant		ENST00000672073.1	NP_001601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACP2	ENST00000672073.1	c.639+94C>T		intron_variant			NM_001610.4	ENSP00000500291	P1

Frequencies

GnomAD3 genomes AF: 0.0342 AC: 5210 AN: 152162 Hom.: 126 Cov.: 33

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0378

Gnomad OTH AF: 0.0320

GnomAD3 exomes AF: 0.0440 AC: 10891 AN: 247402 Hom.: 389 AF XY: 0.0483 AC XY: 6474 AN XY: 134040

Gnomad AFR exome AF: 0.0236

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.0143

Gnomad EAS exome AF: 0.0384

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.0495

Gnomad NFE exome AF: 0.0389

Gnomad OTH exome AF: 0.0341

GnomAD4 exome AF: 0.0409 AC: 48806 AN: 1193098 Hom.: 1370 Cov.: 19 AF XY: 0.0435 AC XY: 26359 AN XY: 605800

Gnomad4 AFR exome AF: 0.0236

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.0145

Gnomad4 EAS exome AF: 0.0349

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0498

Gnomad4 NFE exome AF: 0.0367

Gnomad4 OTH exome AF: 0.0412

GnomAD4 genome AF: 0.0342 AC: 5207 AN: 152280 Hom.: 124 Cov.: 33 AF XY: 0.0358 AC XY: 2663 AN XY: 74448

Gnomad4 AFR AF: 0.0227

Gnomad4 AMR AF: 0.0166

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.0424

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0378

Gnomad4 OTH AF: 0.0321

Alfa AF: 0.0363 Hom.: 30

Bravo AF: 0.0290

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.61

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: rs11039146; hg19: chr11-47266762;