NM_000236.3:c.88+2425G>C

Variant names:

• chr15-58434545-G-C
• rs261334
• NM_000236.3:c.88+2425G>C

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+2425G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,160 control chromosomes in the GnomAD database, including 41,082 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 0.73 (41082 hom., cov: 33)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 54 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]

ALDH1A2 Gene-Disease associations (from GenCC):

• diaphragmatic hernia 4, with cardiovascular defects

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

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 = 0.784 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	NM_000236.3	MANE Select	c.88+2425G>C		intron	N/A	NP_000227.2	P11150

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.88+2425G>C		intron	N/A	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.88+2425G>C		intron	N/A	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.130+2425G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.730 AC: 111038 AN: 152042 Hom.: 41048 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.730 AC: 111117 AN: 152160 Hom.: 41082 Cov.: 33 AF XY: 0.727 AC XY: 54050 AN XY: 74396

African (AFR) AF: 0.663 AC: 27529 AN: 41498

American (AMR) AF: 0.617 AC: 9437 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2859 AN: 3462

East Asian (EAS) AF: 0.635 AC: 3286 AN: 5172

South Asian (SAS) AF: 0.771 AC: 3717 AN: 4818

European-Finnish (FIN) AF: 0.752 AC: 7975 AN: 10598

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53710 AN: 67992

Other (OTH) AF: 0.734 AC: 1553 AN: 2116

Alfa AF: 0.782 Hom.: 23021

Bravo AF: 0.714

Asia WGS AF: 0.686 AC: 2385 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	2.2
DANN	Benign	0.34
PhyloP100		0.020
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: rs261334; hg19: chr15-58726744;