rs11630220

chr15-58515975-G-Achr15-58515975-G-C

Variant summary

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

The NM_000236.3(LIPC):c.89-22358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 152,110 control chromosomes in the GnomAD database, including 931 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 0.097 (931 hom., cov: 31)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPC	NM_000236.3	c.89-22358G>A		intron_variant		ENST00000299022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPC	ENST00000299022.10	c.89-22358G>A		intron_variant		1	NM_000236.3	P1

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 14764 AN: 151992 Hom.: 931 Cov.: 31

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0400

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.0920

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

GnomAD4 genome AF: 0.0970 AC: 14756 AN: 152110 Hom.: 931 Cov.: 31 AF XY: 0.0937 AC XY: 6971 AN XY: 74358

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.0802

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0394

Gnomad4 SAS AF: 0.0357

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.0910

Alfa AF: 0.0567 Hom.: 96

Bravo AF: 0.0891

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.13
Dann	Benign	0.54

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: rs11630220; hg19: chr15-58808174;