15-58560910-A-G

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.1098A>G(p.Thr366Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 1,530,340 control chromosomes in the GnomAD database, including 728,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68368 hom., cov: 32)

Exomes 𝑓: 0.98 ( 659876 hom. )

Consequence

LIPC
NM_000236.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.123

Publications

26 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=-0.89).

BP6

Variant 15-58560910-A-G is Benign according to our data. Variant chr15-58560910-A-G is described in ClinVar as Benign. ClinVar VariationId is 316674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.123 with no splicing effect.

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.1098A>G	p.Thr366Thr	synonymous_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.1098A>G	p.Thr366Thr	synonymous_variant	Exon 7 of 9	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes

AF:

0.946

AC:

143958

AN:

152152

Hom.:

68334

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:

0.987

Gnomad FIN

AF:

0.947

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.986

Gnomad OTH

AF:

0.966

GnomAD2 exomes

AF:

0.972

AC:

244309

AN:

251330

AF XY:

0.975

show subpopulations

Gnomad AFR exome

AF:

0.860

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:

0.978

AC:

1348031

AN:

1378070

Hom.:

659876

Cov.:

AF XY:

0.979

AC XY:

675895

AN XY:

690322

show subpopulations

African (AFR)

AF:

0.855

AC:

27192

AN:

31786

American (AMR)

AF:

0.990

AC:

44144

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.998

AC:

25614

AN:

25672

East Asian (EAS)

AF:

0.910

AC:

35750

AN:

39266

South Asian (SAS)

AF:

0.987

AC:

83466

AN:

84564

European-Finnish (FIN)

AF:

0.948

AC:

50603

AN:

53390

Middle Eastern (MID)

AF:

0.987

AC:

5548

AN:

5620

European-Non Finnish (NFE)

AF:

0.985

AC:

1019566

AN:

1035578

Other (OTH)

AF:

0.975

AC:

56148

AN:

57588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

1430

2860

4291

5721

7151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19594

39188

58782

78376

97970

<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:

144044

AN:

152270

Hom.:

68368

Cov.:

AF XY:

0.946

AC XY:

70413

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.857

AC:

35612

AN:

41538

American (AMR)

AF:

0.982

AC:

15018

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.998

AC:

3466

AN:

3472

East Asian (EAS)

AF:

0.936

AC:

4848

AN:

5180

South Asian (SAS)

AF:

0.987

AC:

4763

AN:

4828

European-Finnish (FIN)

AF:

0.947

AC:

10039

AN:

10606

Middle Eastern (MID)

AF:

0.983

AC:

289

AN:

294

European-Non Finnish (NFE)

AF:

0.986

AC:

67051

AN:

68032

Other (OTH)

AF:

0.967

AC:

2046

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

372

744

1117

1489

1861

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:

0.974

Hom.:

293067

Bravo

AF:

0.945

Asia WGS

AF:

0.962

AC:

3346

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

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

-0.89

CADD

Benign

0.12

(source)

DANN

Benign

0.34

PhyloP100

-0.12

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