15-58542542-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000236.3(LIPC):c.465G>T(p.Val155Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,605,242 control chromosomes in the GnomAD database, including 260,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23085 hom., cov: 32)

Exomes 𝑓: 0.57 ( 237249 hom. )

Consequence

LIPC
NM_000236.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.134

Publications

43 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 15-58542542-G-T is Benign according to our data. Variant chr15-58542542-G-T is described in ClinVar as Benign. ClinVar VariationId is 316660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.134 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3 link	c.465G>T	p.Val155Val	synonymous_variant	Exon 4 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.465G>T	p.Val155Val	synonymous_variant	Exon 4 of 9	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83070

AN:

151864

Hom.:

23081

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.729

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.572

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.566

Gnomad FIN

AF:

0.547

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.511

GnomAD2 exomes

AF:

0.533

AC:

133986

AN:

251454

AF XY:

0.542

show subpopulations

Gnomad AFR exome

AF:

0.558

Gnomad AMR exome

AF:

0.423

Gnomad ASJ exome

AF:

0.589

Gnomad EAS exome

AF:

0.247

Gnomad FIN exome

AF:

0.556

Gnomad NFE exome

AF:

0.586

Gnomad OTH exome

AF:

0.542

GnomAD4 exome

AF:

0.566

AC:

822296

AN:

1453260

Hom.:

237249

Cov.:

AF XY:

0.567

AC XY:

409954

AN XY:

723418

show subpopulations

African (AFR)

AF:

0.544

AC:

18117

AN:

33284

American (AMR)

AF:

0.427

AC:

19093

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.591

AC:

15411

AN:

26078

East Asian (EAS)

AF:

0.218

AC:

8649

AN:

39620

South Asian (SAS)

AF:

0.582

AC:

50102

AN:

86078

European-Finnish (FIN)

AF:

0.552

AC:

29402

AN:

53284

Middle Eastern (MID)

AF:

0.569

AC:

3268

AN:

5748

European-Non Finnish (NFE)

AF:

0.584

AC:

645200

AN:

1104414

Other (OTH)

AF:

0.550

AC:

33054

AN:

60068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

16482

32963

49445

65926

82408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17550

35100

52650

70200

87750

<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:

0.547

AC:

83109

AN:

151982

Hom.:

23085

Cov.:

AF XY:

0.543

AC XY:

40309

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.548

AC:

22720

AN:

41442

American (AMR)

AF:

0.471

AC:

7203

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.572

AC:

1986

AN:

3470

East Asian (EAS)

AF:

0.252

AC:

1301

AN:

5160

South Asian (SAS)

AF:

0.566

AC:

2723

AN:

4812

European-Finnish (FIN)

AF:

0.547

AC:

5779

AN:

10564

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.582

AC:

39513

AN:

67944

Other (OTH)

AF:

0.506

AC:

1063

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1946

3892

5838

7784

9730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.568

Hom.:

54280

Bravo

AF:

0.542

Asia WGS

AF:

0.352

AC:

1227

AN:

3478

EpiCase

AF:

0.596

EpiControl

AF:

0.589

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

Aug 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 13, 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

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.38

(source)

DANN

Benign

0.56

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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