11-47245528-C-T

Variant names:

• chr11-47245528-C-T
• rs10838677
• NM_001610.4:c.495G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001610.4(ACP2):​c.495G>A​(p.Leu165Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,614,214 control chromosomes in the GnomAD database, including 1,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (123 hom., cov: 33)
  • Exomes 𝑓: 0.040 (1572 hom.)
• Consequence: ACP2 NM_001610.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.56
• Publications: 9 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 11-47245528-C-T is Benign according to our data. Variant chr11-47245528-C-T is described in ClinVar as Benign. ClinVar VariationId is 558906.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001610.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP2	NM_001610.4	MANE Select	c.495G>A	p.Leu165Leu	synonymous	Exon 5 of 11	NP_001601.1
	ACP2	NM_001357016.2		c.495G>A	p.Leu165Leu	synonymous	Exon 5 of 11	NP_001343945.1
	ACP2	NM_001302489.2		c.411G>A	p.Leu137Leu	synonymous	Exon 5 of 11	NP_001289418.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP2	ENST00000672073.1	MANE Select	c.495G>A	p.Leu165Leu	synonymous	Exon 5 of 11	ENSP00000500291.1
	ACP2	ENST00000256997.9	TSL:1	c.495G>A	p.Leu165Leu	synonymous	Exon 5 of 11	ENSP00000256997.3
	ACP2	ENST00000672636.2		c.495G>A	p.Leu165Leu	synonymous	Exon 5 of 11	ENSP00000500571.2

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5196 AN: 152208 Hom.: 125 Cov.: 33

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.0432

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0316

GnomAD2 exomes AF: 0.0439 AC: 11045 AN: 251460 AF XY: 0.0482

Gnomad AFR exome AF: 0.0234

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.0383

Gnomad FIN exome AF: 0.0500

Gnomad NFE exome AF: 0.0387

Gnomad OTH exome AF: 0.0341

GnomAD4 exome AF: 0.0401 AC: 58666 AN: 1461888 Hom.: 1572 Cov.: 31 AF XY: 0.0425 AC XY: 30938 AN XY: 727248

African (AFR) AF: 0.0234 AC: 783 AN: 33480

American (AMR) AF: 0.0138 AC: 617 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 330 AN: 26136

East Asian (EAS) AF: 0.0352 AC: 1399 AN: 39700

South Asian (SAS) AF: 0.113 AC: 9733 AN: 86256

European-Finnish (FIN) AF: 0.0501 AC: 2676 AN: 53418

Middle Eastern (MID) AF: 0.0295 AC: 170 AN: 5768

European-Non Finnish (NFE) AF: 0.0364 AC: 40444 AN: 1112010

Other (OTH) AF: 0.0416 AC: 2514 AN: 60396

GnomAD4 genome AF: 0.0341 AC: 5193 AN: 152326 Hom.: 123 Cov.: 33 AF XY: 0.0357 AC XY: 2662 AN XY: 74486

African (AFR) AF: 0.0228 AC: 947 AN: 41592

American (AMR) AF: 0.0166 AC: 254 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3468

East Asian (EAS) AF: 0.0425 AC: 220 AN: 5178

South Asian (SAS) AF: 0.118 AC: 569 AN: 4830

European-Finnish (FIN) AF: 0.0465 AC: 494 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0377 AC: 2563 AN: 68020

Other (OTH) AF: 0.0318 AC: 67 AN: 2108

Alfa AF: 0.0347 Hom.: 193

Bravo AF: 0.0289

Asia WGS AF: 0.117 AC: 408 AN: 3478

EpiCase AF: 0.0362

EpiControl AF: 0.0354

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.5
DANN	Benign	0.87
PhyloP100		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10838677; hg19: chr11-47267079;