NM_005357.4:c.298T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005357.4(LIPE):c.298T>C(p.Tyr100His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,614,018 control chromosomes in the GnomAD database, including 2,066 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 1047 hom., cov: 31)

Exomes 𝑓: 0.0078 ( 1019 hom. )

Consequence

LIPE
NM_005357.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.208

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014833629).

BP6

Variant 19-42426852-A-G is Benign according to our data. Variant chr19-42426852-A-G is described in ClinVar as Benign. ClinVar VariationId is 1243216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPE	NM_005357.4 link	c.298T>C	p.Tyr100His	missense_variant	Exon 1 of 10	ENST00000244289.9	NP_005348.2	Q05469-1A8K8W7
LIPE	XM_005258937.4 link	c.298T>C	p.Tyr100His	missense_variant	Exon 1 of 9		XP_005258994.1
LIPE-AS1	NR_073179.1 link	n.1450+1648A>G		intron_variant	Intron 1 of 1
LIPE-AS1	NR_073180.1 link	n.77+29628A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9 link	c.298T>C	p.Tyr100His	missense_variant	Exon 1 of 10	1	NM_005357.4	ENSP00000244289.3		Q05469-1

Frequencies

GnomAD3 genomes

AF:

0.0656

AC:

9977

AN:

152006

Hom.:

1037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0305

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.0533

GnomAD2 exomes

AF:

0.0185

AC:

4643

AN:

251452

AF XY:

0.0135

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.0134

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00162

Gnomad OTH exome

AF:

0.0130

GnomAD4 exome

AF:

0.00778

AC:

11377

AN:

1461894

Hom.:

1019

Cov.:

AF XY:

0.00699

AC XY:

5083

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.237

AC:

7950

AN:

33480

American (AMR)

AF:

0.0148

AC:

661

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00455

AC:

119

AN:

26136

East Asian (EAS)

AF:

0.000277

AC:

AN:

39700

South Asian (SAS)

AF:

0.00208

AC:

179

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0286

AC:

165

AN:

5768

European-Non Finnish (NFE)

AF:

0.00104

AC:

1158

AN:

1112012

Other (OTH)

AF:

0.0188

AC:

1133

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

629

1257

1886

2514

3143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.0659

AC:

10030

AN:

152124

Hom.:

1047

Cov.:

AF XY:

0.0643

AC XY:

4780

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.224

AC:

9306

AN:

41470

American (AMR)

AF:

0.0304

AC:

465

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3472

East Asian (EAS)

AF:

0.000774

AC:

AN:

5168

South Asian (SAS)

AF:

0.00166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00150

AC:

102

AN:

67990

Other (OTH)

AF:

0.0551

AC:

116

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

402

804

1205

1607

2009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0326

Hom.:

480

Bravo

AF:

0.0767

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.226

AC:

997

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.0221

AC:

2688

Asia WGS

AF:

0.0400

AC:

141

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24555826) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.6

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.039

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.29

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.69

PhyloP100

-0.21

PrimateAI

Benign

0.27

PROVEAN

Benign

0.12

REVEL

Benign

0.024

Sift

Benign

0.62

Sift4G

Benign

0.43

Polyphen

0.0

Vest4

0.0090

MPC

0.40

ClinPred

0.00084

GERP RS

-1.8

Varity_R

0.039

gMVP

0.16

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

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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