rs2242066

Variant names:

• chr15-58547138-G-A
• rs2242066
• NM_000236.3:c.808+1163G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000236.3(LIPC):​c.808+1163G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,080 control chromosomes in the GnomAD database, including 2,757 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 0.18 (2757 hom., cov: 32)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• hyperlipidemia due to hepatic triglyceride lipase deficiency

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.808+1163G>A		intron_variant	Intron 5 of 8	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.808+1163G>A		intron_variant	Intron 5 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27826 AN: 151960 Hom.: 2749 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.183 AC: 27852 AN: 152080 Hom.: 2757 Cov.: 32 AF XY: 0.190 AC XY: 14091 AN XY: 74342

African (AFR) AF: 0.210 AC: 8716 AN: 41460

American (AMR) AF: 0.194 AC: 2963 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1374 AN: 5174

South Asian (SAS) AF: 0.308 AC: 1482 AN: 4816

European-Finnish (FIN) AF: 0.244 AC: 2581 AN: 10558

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9934 AN: 68002

Other (OTH) AF: 0.146 AC: 309 AN: 2112

Alfa AF: 0.167 Hom.: 270

Bravo AF: 0.178

Asia WGS AF: 0.268 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2242066; hg19: chr15-58839337;