rs12909325

chr15-58541504-G-Achr15-58541504-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000236.3(LIPC):c.274-281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,472 control chromosomes in the GnomAD database, including 8,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.30 (8542 hom., cov: 29)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 15-58541504-G-A is Benign according to our data. Variant chr15-58541504-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPC	NM_000236.3	c.274-281G>A		intron_variant		ENST00000299022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPC	ENST00000299022.10	c.274-281G>A		intron_variant		1	NM_000236.3	P1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45506 AN: 151358 Hom.: 8549 Cov.: 29

Gnomad AFR AF: 0.0884

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.300 AC: 45480 AN: 151472 Hom.: 8542 Cov.: 29 AF XY: 0.298 AC XY: 22060 AN XY: 73948

Gnomad4 AFR AF: 0.0881

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.0992

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.315

Alfa AF: 0.323 Hom.: 1670

Bravo AF: 0.281

Asia WGS AF: 0.197 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.2
Dann	Benign	0.49

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: rs12909325; hg19: chr15-58833703;