chr2-74528651-A-C

Position:

• chr2-74528651-A-C

Variant summary

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

The NM_181575.5(AUP1):​c.524+100T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,425,506 control chromosomes in the GnomAD database, including 49,073 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 (11582 hom., cov: 33)
  • Exomes 𝑓: 0.20 (37491 hom.)
• Consequence: AUP1 NM_181575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUP1	NM_181575.5	c.524+100T>G		intron_variant		ENST00000377526.4
AUP1	NR_126510.2	n.601+100T>G		intron_variant, non_coding_transcript_variant
AUP1	NR_126511.2	n.797+100T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUP1	ENST00000377526.4	c.524+100T>G		intron_variant		1	NM_181575.5	P1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48797 AN: 152008 Hom.: 11557 Cov.: 33

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.196 AC: 249498 AN: 1273380 Hom.: 37491 Cov.: 19 AF XY: 0.197 AC XY: 124890 AN XY: 634670

Gnomad4 AFR exome AF: 0.616

Gnomad4 AMR exome AF: 0.340

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.840

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.321 AC: 48869 AN: 152126 Hom.: 11582 Cov.: 33 AF XY: 0.323 AC XY: 24014 AN XY: 74408

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.293

Alfa AF: 0.169 Hom.: 3673

Bravo AF: 0.352

Asia WGS AF: 0.581 AC: 2015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.77

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: rs10779958; hg19: chr2-74755778;