rs10779958

Variant names:

• chr2-74528651-A-C
• rs10779958
• NM_181575.5:c.524+100T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-74528651-A-C
• chr2-74528651-A-T

Variant summary

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

The ENST00000377526.4(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 ENST00000377526.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662
• Publications: 19 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 (BayesDel_noAF=-0.8).
• 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: ENST00000377526.4. 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.524+100T>G		intron	N/A	NP_853553.1
	AUP1	NR_126510.2		n.601+100T>G		intron	N/A
	AUP1	NR_126511.2		n.797+100T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUP1	ENST00000377526.4	TSL:1 MANE Select	c.524+100T>G		intron	N/A	ENSP00000366748.3
	AUP1	ENST00000425118.5	TSL:1	n.524+100T>G		intron	N/A	ENSP00000403430.1
	AUP1	ENST00000463900.5	TSL:1	n.788+100T>G		intron	N/A

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

African (AFR) AF: 0.616 AC: 17368 AN: 28182

American (AMR) AF: 0.340 AC: 11527 AN: 33930

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 3425 AN: 21680

East Asian (EAS) AF: 0.840 AC: 31208 AN: 37146

South Asian (SAS) AF: 0.293 AC: 21583 AN: 73670

European-Finnish (FIN) AF: 0.143 AC: 7210 AN: 50248

Middle Eastern (MID) AF: 0.203 AC: 897 AN: 4428

European-Non Finnish (NFE) AF: 0.148 AC: 143639 AN: 970634

Other (OTH) AF: 0.236 AC: 12641 AN: 53462

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

African (AFR) AF: 0.605 AC: 25094 AN: 41460

American (AMR) AF: 0.328 AC: 5011 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3464

East Asian (EAS) AF: 0.831 AC: 4300 AN: 5176

South Asian (SAS) AF: 0.324 AC: 1566 AN: 4826

European-Finnish (FIN) AF: 0.140 AC: 1489 AN: 10606

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9977 AN: 67980

Other (OTH) AF: 0.293 AC: 619 AN: 2114

Alfa AF: 0.221 Hom.: 10081

Bravo AF: 0.352

Asia WGS AF: 0.581 AC: 2015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.77
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10779958; hg19: chr2-74755778;