11-47246999-T-G

Position:

• chr11-47246999-T-G

Variant summary

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

The NM_001610.4(ACP2):​c.297+642A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,002 control chromosomes in the GnomAD database, including 13,211 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 0.40 (13211 hom., cov: 32)
• Consequence: ACP2 NM_001610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACP2	NM_001610.4	c.297+642A>C		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+642A>C		intron_variant			NM_001610.4	ENSP00000500291.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60261 AN: 151884 Hom.: 13201 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.338

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.397 AC: 60302 AN: 152002 Hom.: 13211 Cov.: 32 AF XY: 0.407 AC XY: 30203 AN XY: 74288

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.334

Alfa AF: 0.353 Hom.: 1284

Bravo AF: 0.396

Asia WGS AF: 0.548 AC: 1904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.27

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: rs7129661; hg19: chr11-47268550;