Genetic Variant AUP1:n.490C>G (chr2-74529049-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000463900.5(AUP1):n.490C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,607,370 control chromosomes in the GnomAD database, including 53,617 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 0.32 ( 11486 hom., cov: 33)

Exomes 𝑓: 0.20 ( 42131 hom. )

Consequence

AUP1
ENST00000463900.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.851

Publications

18 publications found

Variant links:

Genes affected

AUP1 (HGNC:891): (AUP1 lipid droplet regulating VLDL assembly factor) The protein encoded this gene is involved in several pathways including quality control of misfolded proteins in the endoplasmic reticulum and lipid droplet accumulation. Lipid droplets are organelles in the cytoplasm that store neutral lipids such as cholesterol esters and trigylycerides to prevent the overabundance of free cholesterol and fatty acids in cells, but also to act as storage for other metabolic processes, such as membrane biogenesis. Reduced expression of this gene results in reduced lipid droplet clustering, a function that is dependent on ubiquitination of the protein. This protein contains multiple domains including a hydrophobic N-terminal domain, an acetyltranferase domain, a ubiquitin-binding CUE domain, and a UBE2B2-binding domain (G2BR). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

AUP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.007).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AUP1	NM_181575.5 link	c.339+83C>G	intron_variant	Intron 3 of 11	ENST00000377526.4	NP_853553.1
AUP1	NR_126511.2 link	n.499C>G	non_coding_transcript_exon_variant	Exon 3 of 11
AUP1	NR_126510.2 link	n.416+83C>G	intron_variant	Intron 3 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUP1	ENST00000377526.4 link	c.339+83C>G		intron_variant	Intron 3 of 11	1	NM_181575.5	ENSP00000366748.3

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48606

AN:

152030

Hom.:

11462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.831

Gnomad SAS

AF:

0.313

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.289

GnomAD2 exomes

AF:

0.273

AC:

67491

AN:

247054

AF XY:

0.261

show subpopulations

Gnomad AFR exome

AF:

0.618

Gnomad AMR exome

AF:

0.338

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.849

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.196

AC:

285129

AN:

1455222

Hom.:

42131

Cov.:

AF XY:

0.196

AC XY:

142012

AN XY:

724316

show subpopulations

African (AFR)

AF:

0.614

AC:

20471

AN:

33328

American (AMR)

AF:

0.340

AC:

15129

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

4122

AN:

26096

East Asian (EAS)

AF:

0.843

AC:

33413

AN:

39650

South Asian (SAS)

AF:

0.283

AC:

24312

AN:

85998

European-Finnish (FIN)

AF:

0.143

AC:

7621

AN:

53342

Middle Eastern (MID)

AF:

0.201

AC:

1153

AN:

5750

European-Non Finnish (NFE)

AF:

0.149

AC:

164741

AN:

1106364

Other (OTH)

AF:

0.235

AC:

14167

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

11586

23172

34758

46344

57930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6474

12948

19422

25896

32370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.320

AC:

48676

AN:

152148

Hom.:

11486

Cov.:

AF XY:

0.321

AC XY:

23893

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.603

AC:

24986

AN:

41452

American (AMR)

AF:

0.326

AC:

4980

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

541

AN:

3470

East Asian (EAS)

AF:

0.831

AC:

4289

AN:

5160

South Asian (SAS)

AF:

0.314

AC:

1515

AN:

4830

European-Finnish (FIN)

AF:

0.140

AC:

1482

AN:

10594

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.147

AC:

9997

AN:

68030

Other (OTH)

AF:

0.291

AC:

614

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1364

2729

4093

5458

6822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.131

Hom.:

405

Bravo

AF:

0.351

Asia WGS

AF:

0.572

AC:

1986

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.9

(source)

DANN

Benign

0.76

PhyloP100

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over