rs3829462

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000236.3(LIPC):c.1068C>A(p.Phe356Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 1,222,610 control chromosomes in the GnomAD database, including 576,991 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68390 hom., cov: 32)

Exomes 𝑓: 0.97 ( 508601 hom. )

Consequence

LIPC
NM_000236.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.54

Publications

47 publications found

Variant links:

Genes affected

LIPC (HGNC:6619): (lipase C, hepatic type) Enables phospholipase A1 activity and triglyceride lipase activity. Involved in several processes, including lipid homeostasis; plasma lipoprotein particle remodeling; and triglyceride catabolic process. Located in extracellular space. Implicated in several diseases, including Alzheimer's disease; coronary artery disease; familial combined hyperlipidemia; peripheral vascular disease; and type 2 diabetes mellitus. Biomarker of hyperinsulinism; obesity; and type 1 diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

LIPC Gene-Disease associations (from GenCC):

hyperlipidemia due to hepatic triglyceride lipase deficiency
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

LIPC 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=1.5836674E-6).

BP6

Variant 15-58560880-C-A is Benign according to our data. Variant chr15-58560880-C-A is described in ClinVar as Benign. ClinVar VariationId is 316673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3 link	c.1068C>A	p.Phe356Leu	missense_variant	Exon 7 of 9	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10 link	c.1068C>A	p.Phe356Leu	missense_variant	Exon 7 of 9	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes

AF:

0.946

AC:

143983

AN:

152158

Hom.:

68356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.858

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.982

Gnomad ASJ

AF:

0.998

Gnomad EAS

AF:

0.936

Gnomad SAS

AF:

0.986

Gnomad FIN

AF:

0.946

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.986

Gnomad OTH

AF:

0.967

GnomAD2 exomes

AF:

0.972

AC:

244028

AN:

251044

AF XY:

0.975

show subpopulations

Gnomad AFR exome

AF:

0.861

Gnomad AMR exome

AF:

0.991

Gnomad ASJ exome

AF:

0.997

Gnomad EAS exome

AF:

0.942

Gnomad FIN exome

AF:

0.949

Gnomad NFE exome

AF:

0.985

Gnomad OTH exome

AF:

0.981

GnomAD4 exome

AF:

0.974

AC:

1042863

AN:

1070334

Hom.:

508601

Cov.:

AF XY:

0.976

AC XY:

537307

AN XY:

550598

show subpopulations

African (AFR)

AF:

0.842

AC:

22591

AN:

26844

American (AMR)

AF:

0.989

AC:

43799

AN:

44264

Ashkenazi Jewish (ASJ)

AF:

0.998

AC:

23651

AN:

23708

East Asian (EAS)

AF:

0.908

AC:

34471

AN:

37944

South Asian (SAS)

AF:

0.986

AC:

77211

AN:

78272

European-Finnish (FIN)

AF:

0.948

AC:

50514

AN:

53298

Middle Eastern (MID)

AF:

0.986

AC:

4997

AN:

5068

European-Non Finnish (NFE)

AF:

0.981

AC:

739514

AN:

753490

Other (OTH)

AF:

0.972

AC:

46115

AN:

47446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

Heterozygous variant carriers

1226

2452

3677

4903

6129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12072

24144

36216

48288

60360

<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:

0.946

AC:

144068

AN:

152276

Hom.:

68390

Cov.:

AF XY:

0.946

AC XY:

70435

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.858

AC:

35622

AN:

41524

American (AMR)

AF:

0.982

AC:

15022

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.998

AC:

3466

AN:

3472

East Asian (EAS)

AF:

0.936

AC:

4848

AN:

5180

South Asian (SAS)

AF:

0.986

AC:

4762

AN:

4828

European-Finnish (FIN)

AF:

0.946

AC:

10048

AN:

10616

Middle Eastern (MID)

AF:

0.986

AC:

290

AN:

294

European-Non Finnish (NFE)

AF:

0.986

AC:

67051

AN:

68032

Other (OTH)

AF:

0.967

AC:

2047

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

363

726

1088

1451

1814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.973

Hom.:

292541

Bravo

AF:

0.945

TwinsUK

AF:

0.984

AC:

3650

ALSPAC

AF:

0.985

AC:

3798

ESP6500AA

AF:

0.867

AC:

3801

ESP6500EA

AF:

0.985

AC:

8458

ExAC

AF:

0.969

AC:

117614

Asia WGS

AF:

0.962

AC:

3345

AN:

3478

EpiCase

AF:

0.987

EpiControl

AF:

0.987

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27884173, 8732782, 20981092, 19428034) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Hyperlipidemia due to hepatic triglyceride lipase deficiency

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

T;.;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.058

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.60

T;T;.;T

MetaRNN

Benign

0.0000016

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

L;.;L;.

PhyloP100

3.5

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.49

T;T;T;T

Sift4G

Benign

0.68

T;T;T;T

Polyphen

0.13

B;.;B;B

Vest4

0.13

MutPred

0.50

Loss of methylation at K357 (P = 0.0317);Loss of methylation at K357 (P = 0.0317);Loss of methylation at K357 (P = 0.0317);.;

MPC

0.11

ClinPred

0.014

GERP RS

3.9

Varity_R

0.22

gMVP

0.58

Mutation Taster

=97/3

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