chr11-47248704-C-T

Position:

chr11-47248704-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001610.4(ACP2):c.86G>A(p.Arg29Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,610,240 control chromosomes in the GnomAD database, including 102,781 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.41 ( 13968 hom., cov: 32)

Exomes 𝑓: 0.33 ( 88813 hom. )

Consequence

ACP2
NM_001610.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.35

Variant links:

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 links:

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]

NR1H3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.5510478E-6).

BP6

Variant 11-47248704-C-T is Benign according to our data. Variant chr11-47248704-C-T is described in ClinVar as [Benign]. Clinvar id is 558909.Status of the report is criteria_provided_single_submitter, 1 stars.

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	UniProt
ACP2	NM_001610.4 linkuse as main transcript	c.86G>A	p.Arg29Gln	missense_variant	1/11	ENST00000672073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP2	ENST00000672073.1 linkuse as main transcript	c.86G>A	p.Arg29Gln	missense_variant	1/11		NM_001610.4	P1	P11117-1

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61611

AN:

152012

Hom.:

13953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.746

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.343

GnomAD3 exomes

AF:

0.392

AC:

95049

AN:

242358

Hom.:

21059

AF XY:

0.383

AC XY:

50337

AN XY:

131300

show subpopulations

Gnomad AFR exome

AF:

0.573

Gnomad AMR exome

AF:

0.437

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.757

Gnomad SAS exome

AF:

0.456

Gnomad FIN exome

AF:

0.417

Gnomad NFE exome

AF:

0.292

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

AF:

0.335

AC:

488164

AN:

1458110

Hom.:

88813

Cov.:

AF XY:

0.336

AC XY:

243674

AN XY:

724988

show subpopulations

Gnomad4 AFR exome

AF:

0.573

Gnomad4 AMR exome

AF:

0.426

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.742

Gnomad4 SAS exome

AF:

0.458

Gnomad4 FIN exome

AF:

0.408

Gnomad4 NFE exome

AF:

0.299

Gnomad4 OTH exome

AF:

0.344

GnomAD4 genome

AF:

0.405

AC:

61660

AN:

152130

Hom.:

13968

Cov.:

AF XY:

0.415

AC XY:

30845

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.569

Gnomad4 AMR

AF:

0.360

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.747

Gnomad4 SAS

AF:

0.463

Gnomad4 FIN

AF:

0.427

Gnomad4 NFE

AF:

0.298

Gnomad4 OTH

AF:

0.339

Alfa

AF:

0.313

Hom.:

16309

Bravo

AF:

0.407

TwinsUK

AF:

0.290

AC:

1074

ALSPAC

AF:

0.306

AC:

1179

ESP6500AA

AF:

0.559

AC:

2452

ESP6500EA

AF:

0.288

AC:

2478

ExAC

AF:

0.386

AC:

46834

Asia WGS

AF:

0.547

AC:

1899

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 26, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.14

T;.;T;T;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.047

T;T;T;.;T

MetaRNN

Benign

0.0000026

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.69

N;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Benign

0.48

PROVEAN

Benign

0.78

N;N;N;N;N

REVEL

Benign

0.075

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.82

T;T;T;.;T

Polyphen

0.0

B;B;B;.;.

Vest4

0.040

MPC

0.41

ClinPred

0.034

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.041

gMVP

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over