Variant 2-74529115-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181575.5(AUP1):c.339+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,614,192 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 118 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 115 hom. )

Consequence

AUP1
NM_181575.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.397

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 2-74529115-G-A is Benign according to our data. Variant chr2-74529115-G-A is described in ClinVar as [Benign]. Clinvar id is 1261136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
AUP1	NM_181575.5 linkuse as main transcript	c.339+17C>T	intron_variant		ENST00000377526.4
AUP1	NR_126511.2 linkuse as main transcript	n.433C>T	non_coding_transcript_exon_variant	3/11
AUP1	NR_126510.2 linkuse as main transcript	n.416+17C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUP1	ENST00000377526.4 linkuse as main transcript	c.339+17C>T		intron_variant		1	NM_181575.5	P1	Q9Y679-2

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3346

AN:

152220

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0764

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00541

AC:

1349

AN:

249416

Hom.:

AF XY:

0.00410

AC XY:

555

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.0777

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.00218

AC:

3181

AN:

1461854

Hom.:

115

Cov.:

AF XY:

0.00192

AC XY:

1399

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0775

Gnomad4 AMR exome

AF:

0.00378

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000809

Gnomad4 OTH exome

AF:

0.00457

GnomAD4 genome

AF:

0.0220

AC:

3347

AN:

152338

Hom.:

118

Cov.:

AF XY:

0.0213

AC XY:

1590

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0762

Gnomad4 AMR

AF:

0.00914

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0142

Hom.:

Bravo

AF:

0.0243

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over