15-58545811-A-G

Position:

chr15-58545811-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000236.3(LIPC):c.644A>G(p.Asn215Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,613,832 control chromosomes in the GnomAD database, including 150,437 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 0.49 ( 19950 hom., cov: 33)

Exomes 𝑓: 0.41 ( 130487 hom. )

Consequence

LIPC
NM_000236.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.06

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=9.311974E-6).

BP6

Variant 15-58545811-A-G is Benign according to our data. Variant chr15-58545811-A-G is described in ClinVar as [Benign]. Clinvar id is 316665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-58545811-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPC	NM_000236.3 linkuse as main transcript	c.644A>G	p.Asn215Ser	missense_variant	5/9	ENST00000299022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPC	ENST00000299022.10 linkuse as main transcript	c.644A>G	p.Asn215Ser	missense_variant	5/9	1	NM_000236.3	P1

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

74031

AN:

151956

Hom.:

19910

Cov.:

show subpopulations

Gnomad AFR

AF:

0.674

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.829

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.438

GnomAD3 exomes

AF:

0.473

AC:

118936

AN:

251460

Hom.:

30887

AF XY:

0.464

AC XY:

63057

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.680

Gnomad AMR exome

AF:

0.548

Gnomad ASJ exome

AF:

0.326

Gnomad EAS exome

AF:

0.830

Gnomad SAS exome

AF:

0.555

Gnomad FIN exome

AF:

0.484

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.407

AC:

595410

AN:

1461758

Hom.:

130487

Cov.:

AF XY:

0.409

AC XY:

297505

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.687

Gnomad4 AMR exome

AF:

0.543

Gnomad4 ASJ exome

AF:

0.330

Gnomad4 EAS exome

AF:

0.882

Gnomad4 SAS exome

AF:

0.550

Gnomad4 FIN exome

AF:

0.483

Gnomad4 NFE exome

AF:

0.363

Gnomad4 OTH exome

AF:

0.422

GnomAD4 genome

AF:

0.487

AC:

74126

AN:

152074

Hom.:

19950

Cov.:

AF XY:

0.495

AC XY:

36811

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.674

Gnomad4 AMR

AF:

0.489

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.830

Gnomad4 SAS

AF:

0.564

Gnomad4 FIN

AF:

0.483

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.383

Hom.:

22644

Bravo

AF:

0.497

TwinsUK

AF:

0.362

AC:

1343

ALSPAC

AF:

0.364

AC:

1402

ESP6500AA

AF:

0.678

AC:

2974

ESP6500EA

AF:

0.363

AC:

3117

ExAC

AF:

0.470

AC:

57087

Asia WGS

AF:

0.686

AC:

2382

AN:

3478

EpiCase

AF:

0.342

EpiControl

AF:

0.342

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 10, 2018	This variant is associated with the following publications: (PMID: 1883393, 12777476, 22464213, 25361584, 17080261, 19734193, 17137217, 19399022, 20981092, 18364377) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

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

0.060

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

2.7

DANN

Benign

0.95

DEOGEN2

Uncertain

0.49

T;.;T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.051

T;T;.;T

MetaRNN

Benign

0.0000093

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.;L;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.055

T;T;T;T

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.0030

B;.;B;B

Vest4

0.022

MPC

0.060

ClinPred

0.0072

GERP RS

-0.071

Varity_R

0.11

gMVP

0.68

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

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