rs6078

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.283G>A(p.Val95Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 1,613,264 control chromosomes in the GnomAD database, including 3,759 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. V95L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.059 ( 504 hom., cov: 32)

Exomes 𝑓: 0.044 ( 3255 hom. )

Consequence

LIPC
NM_000236.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.976

Publications

41 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

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=0.0016957223).

BP6

Variant 15-58541794-G-A is Benign according to our data. Variant chr15-58541794-G-A is described in ClinVar as Benign. ClinVar VariationId is 316656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	NM_000236.3	MANE Select	c.283G>A	p.Val95Met	missense	Exon 3 of 9	NP_000227.2	P11150

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIPC	ENST00000299022.10	TSL:1 MANE Select	c.283G>A	p.Val95Met	missense	Exon 3 of 9	ENSP00000299022.5	P11150
LIPC	ENST00000414170.7	TSL:1	c.283G>A	p.Val95Met	missense	Exon 4 of 10	ENSP00000395569.3	E7EUJ1
LIPC	ENST00000559845.5	TSL:1	n.140G>A		non_coding_transcript_exon	Exon 2 of 7

Frequencies

GnomAD3 genomes

AF:

0.0584

AC:

8890

AN:

152096

Hom.:

502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0730

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0522

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.0563

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0297

Gnomad OTH

AF:

0.0522

GnomAD2 exomes

AF:

0.0714

AC:

17826

AN:

249720

AF XY:

0.0696

show subpopulations

Gnomad AFR exome

AF:

0.0764

Gnomad AMR exome

AF:

0.0711

Gnomad ASJ exome

AF:

0.0186

Gnomad EAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.0541

Gnomad NFE exome

AF:

0.0297

Gnomad OTH exome

AF:

0.0476

GnomAD4 exome

AF:

0.0443

AC:

64709

AN:

1461048

Hom.:

3255

Cov.:

AF XY:

0.0455

AC XY:

33089

AN XY:

726764

show subpopulations

African (AFR)

AF:

0.0767

AC:

2568

AN:

33462

American (AMR)

AF:

0.0670

AC:

2991

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.0205

AC:

535

AN:

26118

East Asian (EAS)

AF:

0.288

AC:

11428

AN:

39662

South Asian (SAS)

AF:

0.102

AC:

8769

AN:

86094

European-Finnish (FIN)

AF:

0.0555

AC:

2951

AN:

53178

Middle Eastern (MID)

AF:

0.0247

AC:

141

AN:

5700

European-Non Finnish (NFE)

AF:

0.0287

AC:

31895

AN:

1111818

Other (OTH)

AF:

0.0568

AC:

3431

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

3486

6973

10459

13946

17432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1474

2948

4422

5896

7370

<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:

0.0587

AC:

8929

AN:

152216

Hom.:

504

Cov.:

AF XY:

0.0629

AC XY:

4684

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0735

AC:

3052

AN:

41524

American (AMR)

AF:

0.0523

AC:

800

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3470

East Asian (EAS)

AF:

0.322

AC:

1660

AN:

5158

South Asian (SAS)

AF:

0.111

AC:

535

AN:

4818

European-Finnish (FIN)

AF:

0.0563

AC:

597

AN:

10610

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0298

AC:

2024

AN:

68022

Other (OTH)

AF:

0.0578

AC:

122

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

408

815

1223

1630

2038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0438

Hom.:

1069

Bravo

AF:

0.0607

TwinsUK

AF:

0.0297

AC:

110

ALSPAC

AF:

0.0291

AC:

112

ESP6500AA

AF:

0.0746

AC:

327

ESP6500EA

AF:

0.0278

AC:

239

ExAC

AF:

0.0700

AC:

8500

Asia WGS

AF:

0.235

AC:

815

AN:

3478

EpiCase

AF:

0.0263

EpiControl

AF:

0.0287

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hyperlipidemia due to hepatic triglyceride lipase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.0010

(source)

DANN

Benign

0.077

DEOGEN2

Benign

0.31

Eigen

Benign

-3.2

Eigen_PC

Benign

-3.2

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.075

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.0

PhyloP100

-0.98

PrimateAI

Benign

0.25

PROVEAN

Benign

2.0

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.12

Vest4

0.082

MPC

0.072

ClinPred

0.013

GERP RS

-9.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.028

gMVP

0.27

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over