15-58542542-G-T

Position:

• chr15-58542542-G-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.465G>T​(p.Val155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,605,242 control chromosomes in the GnomAD database, including 260,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23085 hom., cov: 32)
  • Exomes 𝑓: 0.57 (237249 hom.)
• Consequence: LIPC NM_000236.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.134

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=-0.9).
• BP6: Variant 15-58542542-G-T is Benign according to our data. Variant chr15-58542542-G-T is described in ClinVar as [Benign]. Clinvar id is 316660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-58542542-G-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.134 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPC	NM_000236.3	c.465G>T	p.Val155=	synonymous_variant	4/9	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.465G>T	p.Val155=	synonymous_variant	4/9	1	NM_000236.3	ENSP00000299022	P1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83070 AN: 151864 Hom.: 23081 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.511

GnomAD3 exomes AF: 0.533 AC: 133986 AN: 251454 Hom.: 37158 AF XY: 0.542 AC XY: 73645 AN XY: 135906

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.589

Gnomad EAS exome AF: 0.247

Gnomad SAS exome AF: 0.581

Gnomad FIN exome AF: 0.556

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.542

GnomAD4 exome AF: 0.566 AC: 822296 AN: 1453260 Hom.: 237249 Cov.: 30 AF XY: 0.567 AC XY: 409954 AN XY: 723418

Gnomad4 AFR exome AF: 0.544

Gnomad4 AMR exome AF: 0.427

Gnomad4 ASJ exome AF: 0.591

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.582

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.584

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.547 AC: 83109 AN: 151982 Hom.: 23085 Cov.: 32 AF XY: 0.543 AC XY: 40309 AN XY: 74280

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.506

Alfa AF: 0.573 Hom.: 43436

Bravo AF: 0.542

Asia WGS AF: 0.352 AC: 1227 AN: 3478

EpiCase AF: 0.596

EpiControl AF: 0.589

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -

not specified Benign:2

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

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	-0.90
CADD	Benign	0.38
DANN	Benign	0.56

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

Other links and lift over

dbSNP: rs690; hg19: chr15-58834741; COSMIC: COSV54420205;