rs4581654

Positions:

• chr15-58521367-A-C
• chr15-58521367-A-G
• chr15-58521367-A-T

Variant summary

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

The NM_000236.3(LIPC):​c.89-16966A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,116 control chromosomes in the GnomAD database, including 35,069 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 0.65 (35001 hom., cov: 30)
  • Exomes 𝑓: 0.76 (68 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPC	NM_000236.3	c.89-16966A>C		intron_variant		ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.89-16966A>C		intron_variant		1	NM_000236.3	ENSP00000299022	P1
	ENST00000561202.1	n.57A>C		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99245 AN: 151778 Hom.: 34996 Cov.: 30

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.718

GnomAD4 exome AF: 0.764 AC: 168 AN: 220 Hom.: 68 Cov.: 0 AF XY: 0.756 AC XY: 130 AN XY: 172

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.755

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.654 AC: 99265 AN: 151896 Hom.: 35001 Cov.: 30 AF XY: 0.656 AC XY: 48687 AN XY: 74234

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.719

Alfa AF: 0.657 Hom.: 3439

Bravo AF: 0.648

Asia WGS AF: 0.712 AC: 2473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.52

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: rs4581654; hg19: chr15-58813566;