Variant chr15-58431476-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000414170.7(LIPC):c.-40-517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 518,670 control chromosomes in the GnomAD database, including 26,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.33 ( 9579 hom., cov: 31)

Exomes 𝑓: 0.27 ( 16528 hom. )

Consequence

LIPC
ENST00000414170.7 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 1.04

Variant links:

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 links:

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]

ALDH1A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	Appris
LIPC	ENST00000414170.7 linkuse as main transcript	c.-40-517C>T	intron_variant	1	ENSP00000395569
LIPC	ENST00000356113.10 linkuse as main transcript	c.-41+325C>T	intron_variant	2	ENSP00000348425	P1
ALDH1A2	ENST00000558239.5 linkuse as main transcript	c.-306-11371G>A	intron_variant	4	ENSP00000453292

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49690

AN:

151838

Hom.:

9546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.506

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.322

GnomAD3 exomes

AF:

0.303

AC:

69477

AN:

229344

Hom.:

12954

AF XY:

0.284

AC XY:

35985

AN XY:

126752

show subpopulations

Gnomad AFR exome

AF:

0.507

Gnomad AMR exome

AF:

0.563

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.378

Gnomad SAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.252

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.272

AC:

99670

AN:

366714

Hom.:

16528

Cov.:

AF XY:

0.260

AC XY:

54624

AN XY:

210268

show subpopulations

Gnomad4 AFR exome

AF:

0.506

Gnomad4 AMR exome

AF:

0.563

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.392

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.248

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.327

AC:

49760

AN:

151956

Hom.:

9579

Cov.:

AF XY:

0.331

AC XY:

24596

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.506

Gnomad4 AMR

AF:

0.425

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.399

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.318

Alfa

AF:

0.229

Hom.:

8772

Bravo

AF:

0.350

Asia WGS

AF:

0.361

AC:

1254

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

High density lipoprotein cholesterol level quantitative trait locus 12

Other:1

association, no assertion criteria provided

literature only

OMIM

Aug 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over