chr11-47245211-G-A

Variant names:

• chr11-47245211-G-A
• rs11039146
• NM_001610.4:c.639+94C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.86).
• 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 rank	MANE	Protein	UniProt
ACP2	NM_001610.4	c.639+94C>T		intron_variant	Intron 6 of 10	ENST00000672073.1	NP_001601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP2	ENST00000672073.1	c.639+94C>T		intron_variant	Intron 6 of 10		NM_001610.4	ENSP00000500291.1

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

GnomAD2 exomes AF: 0.0440 AC: 10891 AN: 247402 AF XY: 0.0483

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 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

African (AFR) AF: 0.0236 AC: 667 AN: 28286

American (AMR) AF: 0.0139 AC: 617 AN: 44374

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 355 AN: 24552

East Asian (EAS) AF: 0.0349 AC: 1341 AN: 38436

South Asian (SAS) AF: 0.113 AC: 9153 AN: 80986

European-Finnish (FIN) AF: 0.0498 AC: 2496 AN: 50112

Middle Eastern (MID) AF: 0.0283 AC: 148 AN: 5236

European-Non Finnish (NFE) AF: 0.0367 AC: 31904 AN: 869558

Other (OTH) AF: 0.0412 AC: 2125 AN: 51558

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

African (AFR) AF: 0.0227 AC: 945 AN: 41548

American (AMR) AF: 0.0166 AC: 254 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.0424 AC: 220 AN: 5186

South Asian (SAS) AF: 0.118 AC: 570 AN: 4826

European-Finnish (FIN) AF: 0.0466 AC: 495 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0378 AC: 2570 AN: 68022

Other (OTH) AF: 0.0321 AC: 68 AN: 2116

Alfa AF: 0.0372 Hom.: 165

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
PhyloP100		-0.23
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: rs11039146; hg19: chr11-47266762;