chr15-58454631-T-C

Position:

• chr15-58454631-T-C

Variant summary

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

The NM_000236.3(LIPC):​c.88+22511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,078 control chromosomes in the GnomAD database, including 10,043 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 0.36 (10039 hom., cov: 33)
  • Exomes 𝑓: 0.42 (4 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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 (HGNC:):

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPC	NM_000236.3	c.88+22511T>C		intron_variant		ENST00000299022.10	NP_000227.2
LIPC-AS1	NR_120338.1	n.209-17719A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.88+22511T>C		intron_variant		1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54621 AN: 151912 Hom.: 10026 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.417 AC: 20 AN: 48 Hom.: 4 Cov.: 0 AF XY: 0.450 AC XY: 18 AN XY: 40

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.360 AC: 54670 AN: 152030 Hom.: 10039 Cov.: 33 AF XY: 0.361 AC XY: 26800 AN XY: 74298

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.371

Alfa AF: 0.345 Hom.: 21822

Bravo AF: 0.376

Asia WGS AF: 0.408 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.4
DANN	Benign	0.73

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: rs3825776; hg19: chr15-58746830;