15-58565746-A-T

Position:

• chr15-58565746-A-T

Variant summary

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

The ENST00000414170.7(LIPC):​c.*456A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 991,876 control chromosomes in the GnomAD database, including 234,532 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 0.60 (28888 hom., cov: 31)
  • Exomes 𝑓: 0.70 (205644 hom.)
• Consequence: LIPC ENST00000414170.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPC	NM_000236.3	c.1388+2023A>T		intron_variant		ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000414170.7	c.*456A>T		3_prime_UTR_variant	10/10	1		ENSP00000395569.3
LIPC	ENST00000299022.10	c.1388+2023A>T		intron_variant		1	NM_000236.3	ENSP00000299022.5
LIPC	ENST00000356113.10	c.1388+2023A>T		intron_variant		2		ENSP00000348425.6
LIPC	ENST00000433326.2	c.1205+2023A>T		intron_variant		2		ENSP00000395002.2

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90665 AN: 151814 Hom.: 28885 Cov.: 31

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.610

GnomAD4 exome AF: 0.697 AC: 585841 AN: 839940 Hom.: 205644 Cov.: 31 AF XY: 0.699 AC XY: 271224 AN XY: 388234

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.704

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.756

Gnomad4 FIN exome AF: 0.729

Gnomad4 NFE exome AF: 0.706

Gnomad4 OTH exome AF: 0.663

GnomAD4 genome AF: 0.597 AC: 90700 AN: 151936 Hom.: 28888 Cov.: 31 AF XY: 0.600 AC XY: 44561 AN XY: 74236

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.608

Alfa AF: 0.646 Hom.: 3877

Bravo AF: 0.577

Asia WGS AF: 0.557 AC: 1939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.50

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: rs3829460; hg19: chr15-58857945;