NM_000236.3:c.88+45264C>T

Variant names:

• chr15-58477384-C-T
• rs4775053
• NM_000236.3:c.88+45264C>T

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+45264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,142 control chromosomes in the GnomAD database, including 1,537 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 0.14 (1537 hom., cov: 32)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 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+45264C>T		intron	N/A	NP_000227.2
	LIPC-AS1	NR_120338.1		n.208+17389G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.88+45264C>T		intron	N/A	ENSP00000299022.5
	LIPC	ENST00000414170.7	TSL:1	c.88+45264C>T		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000559845.5	TSL:1	n.130+45264C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21310 AN: 152024 Hom.: 1533 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0859

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.140 AC: 21319 AN: 152142 Hom.: 1537 Cov.: 32 AF XY: 0.134 AC XY: 10001 AN XY: 74360

African (AFR) AF: 0.137 AC: 5668 AN: 41512

American (AMR) AF: 0.117 AC: 1790 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3470

East Asian (EAS) AF: 0.0857 AC: 444 AN: 5178

South Asian (SAS) AF: 0.0854 AC: 412 AN: 4822

European-Finnish (FIN) AF: 0.107 AC: 1130 AN: 10584

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11026 AN: 67978

Other (OTH) AF: 0.126 AC: 266 AN: 2112

Alfa AF: 0.151 Hom.: 3023

Bravo AF: 0.140

Asia WGS AF: 0.0950 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.74
PhyloP100		-0.70
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: rs4775053; hg19: chr15-58769583;