rs6078

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 316656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-58541794-G-A is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPC	NM_000236.3 linkuse as main transcript	c.283G>A	p.Val95Met	missense_variant	3/9	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10 linkuse as main transcript	c.283G>A	p.Val95Met	missense_variant	3/9	1	NM_000236.3	ENSP00000299022	P1

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

GnomAD3 exomes

AF:

0.0714

AC:

17826

AN:

249720

Hom.:

1418

AF XY:

0.0696

AC XY:

9398

AN XY:

135112

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 SAS exome

AF:

0.101

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

Gnomad4 AFR exome

AF:

0.0767

Gnomad4 AMR exome

AF:

0.0670

Gnomad4 ASJ exome

AF:

0.0205

Gnomad4 EAS exome

AF:

0.288

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.0555

Gnomad4 NFE exome

AF:

0.0287

Gnomad4 OTH exome

AF:

0.0568

GnomAD4 genome

AF:

0.0587

AC:

8929

AN:

152216

Hom.:

504

Cov.:

AF XY:

0.0629

AC XY:

4684

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0735

Gnomad4 AMR

AF:

0.0523

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.322

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.0563

Gnomad4 NFE

AF:

0.0298

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0402

Hom.:

708

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

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 05, 2018	This variant is associated with the following publications: (PMID: 31619059, 10924721, 19428034, 24503134) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hyperlipidemia due to hepatic triglyceride lipase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

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

Benign

0.069

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.0010

DANN

Benign

0.077

DEOGEN2

Benign

0.31

T;.;T

Eigen

Benign

-3.2

Eigen_PC

Benign

-3.2

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.075

T;T;.

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.0

N;.;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

2.0

N;N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.12

B;.;B

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over