Genetic Variant AUP1:c.339+83C>G (chr2-74529049-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181575.5(AUP1):c.339+83C>G variant causes a intron 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
NM_181575.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.851

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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	UniProt
AUP1	NM_181575.5 link	c.339+83C>G	intron_variant	Intron 3 of 11	ENST00000377526.4	NP_853553.1	Q9Y679-2
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		Q9Y679-2

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

GnomAD3 exomes

AF:

0.273

AC:

67491

AN:

247054

Hom.:

14351

AF XY:

0.261

AC XY:

34975

AN XY:

134152

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 SAS exome

AF:

0.286

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

Gnomad4 AFR exome

AF:

0.614

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.158

Gnomad4 EAS exome

AF:

0.843

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.320

AC:

48676

AN:

152148

Hom.:

11486

Cov.:

AF XY:

0.321

AC XY:

23893

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.603

Gnomad4 AMR

AF:

0.326

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.831

Gnomad4 SAS

AF:

0.314

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.291

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

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over