rs12593008

Positions:

• chr15-58468776-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000236.3(LIPC):​c.88+36656C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,062 control chromosomes in the GnomAD database, including 5,061 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 0.25 (5061 hom., cov: 32)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPC	NM_000236.3	c.88+36656C>A		intron_variant		ENST00000299022.10	NP_000227.2
LIPC-AS1	NR_120338.1	n.208+25997G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.88+36656C>A		intron_variant		1	NM_000236.3	ENSP00000299022	P1
LIPC-AS1	ENST00000561083.1	n.208+25997G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38027 AN: 151944 Hom.: 5052 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.250 AC: 38041 AN: 152062 Hom.: 5061 Cov.: 32 AF XY: 0.259 AC XY: 19269 AN XY: 74310

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.259

Alfa AF: 0.258 Hom.: 1317

Bravo AF: 0.229

Asia WGS AF: 0.372 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.6
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs12593008; hg19: chr15-58760975;