15-58516379-C-T

Position:

• chr15-58516379-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000236.3(LIPC):​c.89-21954C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 150,968 control chromosomes in the GnomAD database, including 23,545 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23545 hom., cov: 27)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPC	NM_000236.3	c.89-21954C>T		intron_variant		ENST00000299022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPC	ENST00000299022.10	c.89-21954C>T		intron_variant		1	NM_000236.3	P1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 83613 AN: 150856 Hom.: 23528 Cov.: 27

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.570

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.554 AC: 83655 AN: 150968 Hom.: 23545 Cov.: 27 AF XY: 0.550 AC XY: 40556 AN XY: 73722

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.569

Alfa AF: 0.601 Hom.: 46111

Bravo AF: 0.562

Asia WGS AF: 0.579 AC: 2013 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs4774302; hg19: chr15-58808578;