NM_000236.3:c.89-22358G>A

Variant names:

• chr15-58515975-G-A
• rs11630220
• NM_000236.3:c.89-22358G>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.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
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	NM_000236.3	MANE Select	c.89-22358G>A		intron	N/A	NP_000227.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.89-22358G>A		intron	N/A	ENSP00000299022.5
	LIPC	ENST00000414170.7	TSL:1	c.89-22358G>A		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000559845.5	TSL:1	n.131-25810G>A		intron	N/A

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

African (AFR) AF: 0.0242 AC: 1003 AN: 41504

American (AMR) AF: 0.0802 AC: 1226 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3470

East Asian (EAS) AF: 0.0394 AC: 204 AN: 5182

South Asian (SAS) AF: 0.0357 AC: 172 AN: 4822

European-Finnish (FIN) AF: 0.137 AC: 1448 AN: 10566

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9998 AN: 67982

Other (OTH) AF: 0.0910 AC: 191 AN: 2098

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.54
PhyloP100		-1.6
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: rs11630220; hg19: chr15-58808174;