11-47245257-T-G

Position:

• chr11-47245257-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.639+48A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,590,562 control chromosomes in the GnomAD database, including 40,891 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 0.27 (6870 hom., cov: 32)
  • Exomes 𝑓: 0.19 (34021 hom.)
• Consequence: ACP2 NM_001610.4 intron
• Scores: Splicing: ADA: 0.00009571
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1716715E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACP2	NM_001610.4	c.639+48A>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.639+48A>C		intron_variant			NM_001610.4	ENSP00000500291.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40592 AN: 151832 Hom.: 6865 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.221

GnomAD3 exomes AF: 0.258 AC: 64848 AN: 251090 Hom.: 11531 AF XY: 0.244 AC XY: 33143 AN XY: 135706

Gnomad AFR exome AF: 0.414

Gnomad AMR exome AF: 0.387

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.670

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.149

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.191 AC: 274279 AN: 1438612 Hom.: 34021 Cov.: 28 AF XY: 0.190 AC XY: 136067 AN XY: 717184

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.654

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.267 AC: 40622 AN: 151950 Hom.: 6870 Cov.: 32 AF XY: 0.277 AC XY: 20576 AN XY: 74264

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.218

Alfa AF: 0.170 Hom.: 4537

Bravo AF: 0.275

TwinsUK AF: 0.151 AC: 560

ALSPAC AF: 0.154 AC: 593

ESP6500AA AF: 0.396 AC: 1743

ESP6500EA AF: 0.149 AC: 1282

ExAC AF: 0.249 AC: 30268

Asia WGS AF: 0.349 AC: 1210 AN: 3478

EpiCase AF: 0.142

EpiControl AF: 0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.69
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.000012	T
MetaSVM	Benign	-0.97	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.012
Sift	Benign	0.28	T
Sift4G	Benign	0.13	T
Vest4		0.13
ClinPred		0.0083	T
GERP RS		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000096
dbscSNV1_RF	Benign	0.018
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: rs2242261; hg19: chr11-47266808; COSMIC: COSV57041999; COSMIC: COSV57041999;