rs11071386

Positions:

• chr15-58523121-G-A

Variant summary

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

The NM_000236.3(LIPC):​c.89-15212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,180 control chromosomes in the GnomAD database, including 24,927 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 0.55 (24902 hom., cov: 32)
  • Exomes 𝑓: 0.68 (25 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPC	NM_000236.3	c.89-15212G>A		intron_variant		ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.89-15212G>A		intron_variant		1	NM_000236.3	ENSP00000299022	P1
	ENST00000561202.1	n.1507G>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84005 AN: 151956 Hom.: 24885 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.608

GnomAD4 exome AF: 0.679 AC: 72 AN: 106 Hom.: 25 Cov.: 0 AF XY: 0.741 AC XY: 43 AN XY: 58

Gnomad4 EAS exome AF: 0.833

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.553 AC: 84032 AN: 152074 Hom.: 24902 Cov.: 32 AF XY: 0.557 AC XY: 41405 AN XY: 74336

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.611

Alfa AF: 0.630 Hom.: 42187

Bravo AF: 0.547

Asia WGS AF: 0.593 AC: 2061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
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: rs11071386; hg19: chr15-58815320;