11-47247578-C-T

Variant names:

• chr11-47247578-C-T
• rs45603841
• NM_001610.4:c.297+63G>A

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+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
• Publications: 4 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=-0.82).
• 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 rank	MANE	Protein	UniProt
ACP2	NM_001610.4	c.297+63G>A		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+63G>A		intron_variant	Intron 3 of 10		NM_001610.4	ENSP00000500291.1

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

GnomAD2 exomes AF: 0.0439 AC: 11019 AN: 250792 AF XY: 0.0482

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 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

African (AFR) AF: 0.0233 AC: 774 AN: 33180

American (AMR) AF: 0.0138 AC: 615 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 329 AN: 26012

East Asian (EAS) AF: 0.0351 AC: 1392 AN: 39636

South Asian (SAS) AF: 0.113 AC: 9706 AN: 85994

European-Finnish (FIN) AF: 0.0500 AC: 2668 AN: 53366

Middle Eastern (MID) AF: 0.0296 AC: 170 AN: 5740

European-Non Finnish (NFE) AF: 0.0364 AC: 39984 AN: 1097754

Other (OTH) AF: 0.0416 AC: 2493 AN: 59896

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

African (AFR) AF: 0.0228 AC: 947 AN: 41576

American (AMR) AF: 0.0165 AC: 253 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3472

East Asian (EAS) AF: 0.0426 AC: 221 AN: 5182

South Asian (SAS) AF: 0.118 AC: 571 AN: 4832

European-Finnish (FIN) AF: 0.0465 AC: 494 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0376 AC: 2560 AN: 68026

Other (OTH) AF: 0.0322 AC: 68 AN: 2114

Alfa AF: 0.0368 Hom.: 165

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
PhyloP100		-0.28
Mutation Taster		=100/0	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: rs45603841; hg19: chr11-47269129;