11-47247608-T-C

Variant names:

• chr11-47247608-T-C
• rs4752973
• NM_001610.4:c.297+33A>G

Variant summary

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

The NM_001610.4(ACP2):​c.297+33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,612,838 control chromosomes in the GnomAD database, including 55,410 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 (8261 hom., cov: 33)
  • Exomes 𝑓: 0.23 (47149 hom.)
• Consequence: ACP2 NM_001610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 37 publications found

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]

ACP2 Gene-Disease associations (from GenCC):

• lysosomal acid phosphatase deficiency

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP2	NM_001610.4	c.297+33A>G		intron_variant	Intron 3 of 10	ENST00000672073.1	NP_001601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP2	ENST00000672073.1	c.297+33A>G		intron_variant	Intron 3 of 10		NM_001610.4	ENSP00000500291.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45871 AN: 152030 Hom.: 8261 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.254

GnomAD2 exomes AF: 0.302 AC: 76001 AN: 251358 AF XY: 0.293

Gnomad AFR exome AF: 0.438

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.708

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.226

GnomAD4 exome AF: 0.231 AC: 336694 AN: 1460688 Hom.: 47149 Cov.: 31 AF XY: 0.232 AC XY: 168620 AN XY: 726736

African (AFR) AF: 0.443 AC: 14815 AN: 33458

American (AMR) AF: 0.386 AC: 17248 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3717 AN: 26130

East Asian (EAS) AF: 0.690 AC: 27367 AN: 39690

South Asian (SAS) AF: 0.347 AC: 29957 AN: 86230

European-Finnish (FIN) AF: 0.316 AC: 16889 AN: 53396

Middle Eastern (MID) AF: 0.194 AC: 1117 AN: 5764

European-Non Finnish (NFE) AF: 0.190 AC: 210902 AN: 1110936

Other (OTH) AF: 0.243 AC: 14682 AN: 60366

GnomAD4 genome AF: 0.302 AC: 45898 AN: 152150 Hom.: 8261 Cov.: 33 AF XY: 0.313 AC XY: 23278 AN XY: 74384

African (AFR) AF: 0.436 AC: 18116 AN: 41514

American (AMR) AF: 0.291 AC: 4455 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3470

East Asian (EAS) AF: 0.694 AC: 3580 AN: 5156

South Asian (SAS) AF: 0.355 AC: 1711 AN: 4824

European-Finnish (FIN) AF: 0.342 AC: 3621 AN: 10578

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13230 AN: 67992

Other (OTH) AF: 0.251 AC: 529 AN: 2110

Alfa AF: 0.266 Hom.: 3230

Bravo AF: 0.304

Asia WGS AF: 0.466 AC: 1618 AN: 3478

EpiCase AF: 0.178

EpiControl AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.4
DANN	Benign	0.45
PhyloP100		0.0090
Mutation Taster		=99/1	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: rs4752973; hg19: chr11-47269159; COSMIC: COSV57042677; COSMIC: COSV57042677;