NM_000236.3:c.88+18099G>A

Variant names:

• chr15-58450219-G-A
• rs261336
• NM_000236.3:c.88+18099G>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.88+18099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,162 control chromosomes in the GnomAD database, including 49,753 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 0.81 (49753 hom., cov: 33)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 30 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]

ALDH1A2 (HGNC:15472): (aldehyde dehydrogenase 1 family member A2) This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

LIPC-AS1 (HGNC:52294): (LIPC antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 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.88+18099G>A		intron	N/A	NP_000227.2
	LIPC-AS1	NR_120338.1		n.209-13307C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.88+18099G>A		intron	N/A	ENSP00000299022.5
	LIPC	ENST00000414170.7	TSL:1	c.88+18099G>A		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000559845.5	TSL:1	n.130+18099G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122826 AN: 152044 Hom.: 49692 Cov.: 33

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.808 AC: 122947 AN: 152162 Hom.: 49753 Cov.: 33 AF XY: 0.801 AC XY: 59627 AN XY: 74396

African (AFR) AF: 0.803 AC: 33326 AN: 41516

American (AMR) AF: 0.789 AC: 12062 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2785 AN: 3470

East Asian (EAS) AF: 0.739 AC: 3826 AN: 5174

South Asian (SAS) AF: 0.739 AC: 3563 AN: 4820

European-Finnish (FIN) AF: 0.748 AC: 7912 AN: 10574

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56748 AN: 68004

Other (OTH) AF: 0.793 AC: 1675 AN: 2112

Alfa AF: 0.824 Hom.: 65603

Bravo AF: 0.813

Asia WGS AF: 0.728 AC: 2533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.75
PhyloP100		-1.1
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: rs261336; hg19: chr15-58742418;