ENST00000463900.5:n.490C>G

Variant names:

• chr2-74529049-G-C
• rs2231250
• ENST00000463900.5:n.490C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851
• Publications: 18 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000463900.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUP1	NM_181575.5	MANE Select	c.339+83C>G		intron	N/A	NP_853553.1
	AUP1	NR_126511.2		n.499C>G		non_coding_transcript_exon	Exon 3 of 11
	AUP1	NR_126510.2		n.416+83C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUP1	ENST00000463900.5	TSL:1	n.490C>G		non_coding_transcript_exon	Exon 3 of 11
	AUP1	ENST00000377526.4	TSL:1 MANE Select	c.339+83C>G		intron	N/A	ENSP00000366748.3
	AUP1	ENST00000425118.5	TSL:1	n.339+83C>G		intron	N/A	ENSP00000403430.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48606 AN: 152030 Hom.: 11462 Cov.: 33

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

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.: 34 AF XY: 0.196 AC XY: 142012 AN XY: 724316

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

GnomAD4 genome AF: 0.320 AC: 48676 AN: 152148 Hom.: 11486 Cov.: 33 AF XY: 0.321 AC XY: 23893 AN XY: 74390

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: 59 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9997 AN: 68030

Other (OTH) AF: 0.291 AC: 614 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.9
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)

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

Other links and lift over

dbSNP: rs2231250; hg19: chr2-74756176; COSMIC: COSV51206416; COSMIC: COSV51206416;