rs16940379

Positions:

• chr15-58504046-C-G

Variant summary

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

The ENST00000299022.10(LIPC):​c.89-34287C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,084 control chromosomes in the GnomAD database, including 4,898 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 0.25 (4898 hom., cov: 32)
• Consequence: LIPC ENST00000299022.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPC	NM_000236.3	c.89-34287C>G		intron_variant		ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.89-34287C>G		intron_variant		1	NM_000236.3	ENSP00000299022	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38241 AN: 151966 Hom.: 4895 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.252 AC: 38259 AN: 152084 Hom.: 4898 Cov.: 32 AF XY: 0.244 AC XY: 18113 AN XY: 74338

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.235

Alfa AF: 0.264 Hom.: 679

Bravo AF: 0.247

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.76

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: rs16940379; hg19: chr15-58796245;