dbSNP rs10779958: AUP1:c.524+100T>G (chr2-74528651-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.662

Publications

19 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 (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	Effect	Exon rank	MANE	Protein	UniProt
AUP1	NM_181575.5 link	c.524+100T>G	intron_variant	Intron 4 of 11	ENST00000377526.4	NP_853553.1	Q9Y679-2
AUP1	NR_126510.2 link	n.601+100T>G	intron_variant	Intron 4 of 11
AUP1	NR_126511.2 link	n.797+100T>G	intron_variant	Intron 3 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUP1	ENST00000377526.4 link	c.524+100T>G		intron_variant	Intron 4 of 11	1	NM_181575.5	ENSP00000366748.3		Q9Y679-2

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48797

AN:

152008

Hom.:

11557

Cov.:

show subpopulations

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.:

AF XY:

0.197

AC XY:

124890

AN XY:

634670

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

9356

18711

28067

37422

46778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5506

11012

16518

22024

27530

<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:

0.321

AC:

48869

AN:

152126

Hom.:

11582

Cov.:

AF XY:

0.323

AC XY:

24014

AN XY:

74408

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.147

AC:

9977

AN:

67980

Other (OTH)

AF:

0.293

AC:

619

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1358

2717

4075

5434

6792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.221

Hom.:

10081

Bravo

AF:

0.352

Asia WGS

AF:

0.581

AC:

2015

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.4

(source)

DANN

Benign

0.77

PhyloP100

0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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