rs6082

chr15-58545758-A-Gchr15-58545758-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000236.3(LIPC):c.591A>G(p.Gly197=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,613,402 control chromosomes in the GnomAD database, including 11,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1148 hom., cov: 34)
  • Exomes 𝑓: 0.097 (10164 hom.)
• Consequence: LIPC NM_000236.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.09

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-58545758-A-G is Benign according to our data. Variant chr15-58545758-A-G is described in ClinVar as [Benign]. Clinvar id is 316664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-58545758-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPC	NM_000236.3	c.591A>G	p.Gly197=	synonymous_variant	5/9	ENST00000299022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPC	ENST00000299022.10	c.591A>G	p.Gly197=	synonymous_variant	5/9	1	NM_000236.3	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15825 AN: 151996 Hom.: 1148 Cov.: 34

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.128 AC: 32071 AN: 251258 Hom.: 3276 AF XY: 0.121 AC XY: 16480 AN XY: 135816

Gnomad AFR exome AF: 0.0918

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.0790

Gnomad EAS exome AF: 0.418

Gnomad SAS exome AF: 0.104

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.0781

Gnomad OTH exome AF: 0.0971

GnomAD4 exome AF: 0.0974 AC: 142273 AN: 1461288 Hom.: 10164 Cov.: 40 AF XY: 0.0966 AC XY: 70260 AN XY: 727006

Gnomad4 AFR exome AF: 0.0883

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.0818

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.0800

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.104 AC: 15840 AN: 152114 Hom.: 1148 Cov.: 34 AF XY: 0.108 AC XY: 8030 AN XY: 74342

Gnomad4 AFR AF: 0.0913

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0781

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0831 Hom.: 1197

Bravo AF: 0.112

Asia WGS AF: 0.271 AC: 941 AN: 3478

EpiCase AF: 0.0766

EpiControl AF: 0.0719

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 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	-0.84
Cadd	Benign	3.4
Dann	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

Other links and lift over

dbSNP: rs6082; hg19: chr15-58837957; COSMIC: COSV54422892;