chr11-47246999-T-G

Variant names:

• chr11-47246999-T-G
• rs7129661
• NM_001610.4:c.297+642A>C

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+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
• Publications: 12 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=-0.89).
• 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 rank	MANE	Protein	UniProt
ACP2	NM_001610.4	c.297+642A>C		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+642A>C		intron_variant	Intron 3 of 10		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

African (AFR) AF: 0.536 AC: 22203 AN: 41448

American (AMR) AF: 0.359 AC: 5486 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3464

East Asian (EAS) AF: 0.746 AC: 3862 AN: 5174

South Asian (SAS) AF: 0.466 AC: 2244 AN: 4814

European-Finnish (FIN) AF: 0.428 AC: 4517 AN: 10552

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20310 AN: 67966

Other (OTH) AF: 0.334 AC: 705 AN: 2110

Alfa AF: 0.411 Hom.: 3142

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
PhyloP100		-0.24
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: rs7129661; hg19: chr11-47268550;