chr11-47248385-C-T

Position:

• chr11-47248385-C-T

Variant summary

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

The NM_001610.4(ACP2):​c.115-252G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,472,246 control chromosomes in the GnomAD database, including 35,675 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 0.26 (6317 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29358 hom.)
• Consequence: ACP2 NM_001610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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]

NR1H3 (HGNC:7966): (nuclear receptor subfamily 1 group H member 3) The protein encoded by this gene belongs to the NR1 subfamily of the nuclear receptor superfamily. The NR1 family members are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. This protein is highly expressed in visceral organs, including liver, kidney and intestine. It forms a heterodimer with retinoid X receptor (RXR), and regulates expression of target genes containing retinoid response elements. Studies in mice lacking this gene suggest that it may play an important role in the regulation of cholesterol homeostasis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACP2	NM_001610.4	c.115-252G>A		intron_variant		ENST00000672073.1	NP_001601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACP2	ENST00000672073.1	c.115-252G>A		intron_variant			NM_001610.4	ENSP00000500291	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39225 AN: 151946 Hom.: 6315 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.186 AC: 244965 AN: 1320182 Hom.: 29358 Cov.: 22 AF XY: 0.186 AC XY: 121224 AN XY: 652456

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.654

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.198

GnomAD4 genome AF: 0.258 AC: 39239 AN: 152064 Hom.: 6317 Cov.: 32 AF XY: 0.268 AC XY: 19903 AN XY: 74352

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.211

Alfa AF: 0.213 Hom.: 786

Bravo AF: 0.265

Asia WGS AF: 0.342 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.8
DANN	Benign	0.59

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: rs7118396; hg19: chr11-47269936;