rs34052647

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005357.4(LIPE):c.1831C>T(p.Arg611Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00414 in 1,608,150 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R611H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0067 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 175 hom. )

Consequence

LIPE
NM_005357.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.93

Publications

10 publications found

Variant links:

Genes affected

LIPE (HGNC:6621): (lipase E, hormone sensitive type) The protein encoded by this gene has a long and a short form, generated by use of alternative translational start codons. The long form is expressed in steroidogenic tissues such as testis, where it converts cholesteryl esters to free cholesterol for steroid hormone production. The short form is expressed in adipose tissue, among others, where it hydrolyzes stored triglycerides to free fatty acids. [provided by RefSeq, Jul 2008]

LIPE links:

LIPE-AS1 (HGNC:48589): (LIPE antisense RNA 1)

LIPE-AS1 links:

LOC101930071 (HGNC:):

LOC101930071 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006269008).

BP6

Variant 19-42407617-G-A is Benign according to our data. Variant chr19-42407617-G-A is described in ClinVar as [Benign]. Clinvar id is 2430297.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPE	NM_005357.4 link	c.1831C>T	p.Arg611Cys	missense_variant	Exon 5 of 10	ENST00000244289.9	NP_005348.2	Q05469-1A8K8W7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9 link	c.1831C>T	p.Arg611Cys	missense_variant	Exon 5 of 10	1	NM_005357.4	ENSP00000244289.3		Q05469-1

Frequencies

GnomAD3 genomes

AF:

0.00672

AC:

1022

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0623

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.0131

AC:

3223

AN:

246066

AF XY:

0.0108

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.0542

Gnomad ASJ exome

AF:

0.00311

Gnomad EAS exome

AF:

0.0639

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.000389

Gnomad OTH exome

AF:

0.00973

GnomAD4 exome

AF:

0.00387

AC:

5637

AN:

1455888

Hom.:

175

Cov.:

AF XY:

0.00361

AC XY:

2615

AN XY:

723638

show subpopulations

African (AFR)

AF:

0.000749

AC:

AN:

33358

American (AMR)

AF:

0.0528

AC:

2326

AN:

44028

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

25770

East Asian (EAS)

AF:

0.0617

AC:

2446

AN:

39614

South Asian (SAS)

AF:

0.00199

AC:

170

AN:

85574

European-Finnish (FIN)

AF:

0.0000564

AC:

AN:

53232

Middle Eastern (MID)

AF:

0.000522

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.000263

AC:

292

AN:

1108514

Other (OTH)

AF:

0.00508

AC:

305

AN:

60052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

313

625

938

1250

1563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00674

AC:

1027

AN:

152262

Hom.:

Cov.:

AF XY:

0.00789

AC XY:

587

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

41554

American (AMR)

AF:

0.0375

AC:

574

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.0625

AC:

323

AN:

5170

South Asian (SAS)

AF:

0.00311

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68010

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

100

151

201

251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00414

Hom.:

Bravo

AF:

0.0103

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0108

AC:

1315

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

See cases

Benign:1

Dec 21, 2022

Institute of Human Genetics, University Hospital Muenster

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ACMG categories: BA1 -

LIPE-related disorder

Benign:1

Sep 26, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.48

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.0063

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.7

PhyloP100

4.9

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.32

MPC

1.2

ClinPred

0.048

GERP RS

1.9

PromoterAI

-0.027

Neutral

(source)

Varity_R

0.61

gMVP

0.73

Mutation Taster

=89/11

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

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rs34052647

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over