chr15-58545839-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000236.3(LIPC):c.672C>G(p.Thr224Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,613,898 control chromosomes in the GnomAD database, including 186,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14216 hom., cov: 33)

Exomes 𝑓: 0.48 ( 172007 hom. )

Consequence

LIPC
NM_000236.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.587

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 15-58545839-C-G is Benign according to our data. Variant chr15-58545839-C-G is described in ClinVar as [Benign]. Clinvar id is 316666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-58545839-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.587 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3 link	c.672C>G	p.Thr224Thr	synonymous_variant	Exon 5 of 9	ENST00000299022.10	NP_000227.2	P11150A6H8L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10 link	c.672C>G	p.Thr224Thr	synonymous_variant	Exon 5 of 9	1	NM_000236.3	ENSP00000299022.5		P11150

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

62365

AN:

152008

Hom.:

14216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.548

Gnomad EAS

AF:

0.0732

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.457

GnomAD3 exomes

AF:

0.426

AC:

107114

AN:

251466

Hom.:

24946

AF XY:

0.435

AC XY:

59135

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.240

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.552

Gnomad EAS exome

AF:

0.0749

Gnomad SAS exome

AF:

0.378

Gnomad FIN exome

AF:

0.433

Gnomad NFE exome

AF:

0.521

Gnomad OTH exome

AF:

0.480

GnomAD4 exome

AF:

0.476

AC:

695079

AN:

1461772

Hom.:

172007

Cov.:

AF XY:

0.475

AC XY:

345441

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.241

Gnomad4 AMR exome

AF:

0.382

Gnomad4 ASJ exome

AF:

0.553

Gnomad4 EAS exome

AF:

0.0520

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.433

Gnomad4 NFE exome

AF:

0.509

Gnomad4 OTH exome

AF:

0.459

GnomAD4 genome

AF:

0.410

AC:

62393

AN:

152126

Hom.:

14216

Cov.:

AF XY:

0.404

AC XY:

30076

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.422

Gnomad4 ASJ

AF:

0.548

Gnomad4 EAS

AF:

0.0730

Gnomad4 SAS

AF:

0.367

Gnomad4 FIN

AF:

0.435

Gnomad4 NFE

AF:

0.520

Gnomad4 OTH

AF:

0.452

Alfa

AF:

0.480

Hom.:

13125

Bravo

AF:

0.401

Asia WGS

AF:

0.241

AC:

843

AN:

3478

EpiCase

AF:

0.532

EpiControl

AF:

0.540

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 30, 2018

GeneDx

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.69

CADD

Benign

5.0

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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