chr11-47247578-C-T

Position:

• chr11-47247578-C-T

Variant summary

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

The NM_001610.4(ACP2):​c.297+63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,598,572 control chromosomes in the GnomAD database, including 1,689 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 (123 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1566 hom.)
• Consequence: ACP2 NM_001610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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=-0.82).
• 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.297+63G>A		intron_variant		ENST00000672073.1	NP_001601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACP2	ENST00000672073.1	c.297+63G>A		intron_variant			NM_001610.4	ENSP00000500291	P1

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5196 AN: 152210 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.0433

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0320

GnomAD3 exomes AF: 0.0439 AC: 11019 AN: 250792 Hom.: 392 AF XY: 0.0482 AC XY: 6540 AN XY: 135568

Gnomad AFR exome AF: 0.0233

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.0123

Gnomad EAS exome AF: 0.0383

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.0500

Gnomad NFE exome AF: 0.0388

Gnomad OTH exome AF: 0.0340

GnomAD4 exome AF: 0.0402 AC: 58131 AN: 1446244 Hom.: 1566 Cov.: 27 AF XY: 0.0426 AC XY: 30715 AN XY: 720624

Gnomad4 AFR exome AF: 0.0233

Gnomad4 AMR exome AF: 0.0138

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.0351

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0500

Gnomad4 NFE exome AF: 0.0364

Gnomad4 OTH exome AF: 0.0416

GnomAD4 genome AF: 0.0341 AC: 5193 AN: 152328 Hom.: 123 Cov.: 32 AF XY: 0.0358 AC XY: 2664 AN XY: 74488

Gnomad4 AFR AF: 0.0228

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.0426

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0465

Gnomad4 NFE AF: 0.0376

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0359 Hom.: 30

Bravo AF: 0.0289

Asia WGS AF: 0.117 AC: 409 AN: 3478

EpiCase AF: 0.0362

EpiControl AF: 0.0354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.57

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: rs45603841; hg19: chr11-47269129;