NM_000236.3:c.88+40864T>G

Variant names:

• chr15-58472984-T-G
• rs7182229
• NM_000236.3:c.88+40864T>G

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+40864T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,108 control chromosomes in the GnomAD database, including 54,297 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 0.84 (54297 hom., cov: 31)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.881 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+40864T>G		intron	N/A	NP_000227.2
	LIPC-AS1	NR_120338.1		n.208+21789A>C		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+40864T>G		intron	N/A	ENSP00000299022.5
	LIPC	ENST00000414170.7	TSL:1	c.88+40864T>G		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000559845.5	TSL:1	n.130+40864T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127841 AN: 151988 Hom.: 54256 Cov.: 31

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.841 AC: 127938 AN: 152108 Hom.: 54297 Cov.: 31 AF XY: 0.844 AC XY: 62740 AN XY: 74366

African (AFR) AF: 0.727 AC: 30125 AN: 41446

American (AMR) AF: 0.845 AC: 12931 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3085 AN: 3472

East Asian (EAS) AF: 0.863 AC: 4450 AN: 5158

South Asian (SAS) AF: 0.843 AC: 4070 AN: 4826

European-Finnish (FIN) AF: 0.949 AC: 10064 AN: 10602

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60328 AN: 67996

Other (OTH) AF: 0.841 AC: 1775 AN: 2110

Alfa AF: 0.872 Hom.: 38328

Bravo AF: 0.830

Asia WGS AF: 0.878 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.68
PhyloP100		0.18
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: rs7182229; hg19: chr15-58765183;