rs6074

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000236.3(LIPC):c.1437C>A(p.Thr479=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,608,476 control chromosomes in the GnomAD database, including 24,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T479T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.15 ( 1950 hom., cov: 33)

Exomes 𝑓: 0.16 ( 22633 hom. )

Consequence

LIPC
NM_000236.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.24

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 15-58568764-C-A is Benign according to our data. Variant chr15-58568764-C-A is described in ClinVar as [Benign]. Clinvar id is 316681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-58568764-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 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.1437C>A	p.Thr479=	synonymous_variant	9/9	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LIPC	ENST00000299022.10 linkuse as main transcript	c.1437C>A	p.Thr479=	synonymous_variant	9/9	1	NM_000236.3	ENSP00000299022	P1
LIPC	ENST00000356113.10 linkuse as main transcript	c.1437C>A	p.Thr479=	synonymous_variant	11/11	2		ENSP00000348425	P1
LIPC	ENST00000433326.2 linkuse as main transcript	c.1254C>A	p.Thr418=	synonymous_variant	8/8	2		ENSP00000395002

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22208

AN:

151956

Hom.:

1944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0915

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.193

AC:

48231

AN:

250016

Hom.:

5626

AF XY:

0.196

AC XY:

26504

AN XY:

135154

show subpopulations

Gnomad AFR exome

AF:

0.0930

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.0997

Gnomad EAS exome

AF:

0.262

Gnomad SAS exome

AF:

0.345

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.165

AC:

239746

AN:

1456404

Hom.:

22633

Cov.:

AF XY:

0.169

AC XY:

122784

AN XY:

724748

show subpopulations

Gnomad4 AFR exome

AF:

0.0945

Gnomad4 AMR exome

AF:

0.248

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.281

Gnomad4 SAS exome

AF:

0.340

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.146

AC:

22216

AN:

152072

Hom.:

1950

Cov.:

AF XY:

0.155

AC XY:

11487

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0914

Gnomad4 AMR

AF:

0.175

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.259

Gnomad4 SAS

AF:

0.336

Gnomad4 FIN

AF:

0.242

Gnomad4 NFE

AF:

0.141

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.134

Hom.:

2893

Bravo

AF:

0.136

Asia WGS

AF:

0.273

AC:

946

AN:

3476

EpiCase

AF:

0.129

EpiControl

AF:

0.123

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 17, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Hyperlipidemia due to hepatic triglyceride lipase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

BayesDel_noAF

Benign

-0.26

CADD

Benign

2.0

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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