rs12324517

Positions:

• chr15-58508567-T-C

Variant summary

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

The NM_000236.3(LIPC):​c.89-29766T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,000 control chromosomes in the GnomAD database, including 17,335 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 0.48 (17335 hom., cov: 31)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPC	NM_000236.3	c.89-29766T>C		intron_variant		ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.89-29766T>C		intron_variant		1	NM_000236.3	ENSP00000299022	P1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72264 AN: 151880 Hom.: 17302 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.476 AC: 72341 AN: 152000 Hom.: 17335 Cov.: 31 AF XY: 0.476 AC XY: 35386 AN XY: 74308

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.496

Alfa AF: 0.483 Hom.: 17896

Bravo AF: 0.486

Asia WGS AF: 0.518 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.59

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: rs12324517; hg19: chr15-58800766;