rs1183739

Positions:

chr2-74529421-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_181575.5(AUP1):c.129C>G(p.Leu43=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,588,962 control chromosomes in the GnomAD database, including 18,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1323 hom., cov: 33)

Exomes 𝑓: 0.15 ( 17212 hom. )

Consequence

AUP1
NM_181575.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0510

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:

HTRA2 (HGNC:):

HTRA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 2-74529421-G-C is Benign according to our data. Variant chr2-74529421-G-C is described in ClinVar as [Benign]. Clinvar id is 337116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.051 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUP1	NM_181575.5 linkuse as main transcript	c.129C>G	p.Leu43=	synonymous_variant	2/12	ENST00000377526.4	NP_853553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUP1	ENST00000377526.4 linkuse as main transcript	c.129C>G	p.Leu43=	synonymous_variant	2/12	1	NM_181575.5	ENSP00000366748	P1	Q9Y679-2

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16561

AN:

152216

Hom.:

1324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0268

Gnomad AMI

AF:

0.0527

Gnomad AMR

AF:

0.0653

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0362

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.113

AC:

22950

AN:

202938

Hom.:

1831

AF XY:

0.113

AC XY:

12403

AN XY:

110194

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.0525

Gnomad ASJ exome

AF:

0.110

Gnomad EAS exome

AF:

0.000204

Gnomad SAS exome

AF:

0.0351

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.145

AC:

208548

AN:

1436628

Hom.:

17212

Cov.:

AF XY:

0.142

AC XY:

101399

AN XY:

712454

show subpopulations

Gnomad4 AFR exome

AF:

0.0218

Gnomad4 AMR exome

AF:

0.0531

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.000130

Gnomad4 SAS exome

AF:

0.0365

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.109

AC:

16552

AN:

152334

Hom.:

1323

Cov.:

AF XY:

0.109

AC XY:

8125

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0267

Gnomad4 AMR

AF:

0.0651

Gnomad4 ASJ

AF:

0.110

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0358

Gnomad4 FIN

AF:

0.250

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.142

Hom.:

578

Bravo

AF:

0.0913

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Jun 26, 2018	- -

Parkinson disease 13, autosomal dominant, susceptibility to

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.6

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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