15-58434545-G-C

Variant summary

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

The NM_000236.3(LIPC):​c.88+2425G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,160 control chromosomes in the GnomAD database, including 41,082 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 0.73 ( 41082 hom., cov: 33)

Consequence

LIPC
NM_000236.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0200
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]
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]

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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=-0.9).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LIPCNM_000236.3 linkc.88+2425G>C intron_variant Intron 1 of 8 ENST00000299022.10 NP_000227.2 P11150A6H8L5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LIPCENST00000299022.10 linkc.88+2425G>C intron_variant Intron 1 of 8 1 NM_000236.3 ENSP00000299022.5 P11150

Frequencies

GnomAD3 genomes
AF:
0.730
AC:
111038
AN:
152042
Hom.:
41048
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.663
Gnomad AMI
AF:
0.889
Gnomad AMR
AF:
0.618
Gnomad ASJ
AF:
0.826
Gnomad EAS
AF:
0.635
Gnomad SAS
AF:
0.771
Gnomad FIN
AF:
0.752
Gnomad MID
AF:
0.820
Gnomad NFE
AF:
0.790
Gnomad OTH
AF:
0.730
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.730
AC:
111117
AN:
152160
Hom.:
41082
Cov.:
33
AF XY:
0.727
AC XY:
54050
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.663
Gnomad4 AMR
AF:
0.617
Gnomad4 ASJ
AF:
0.826
Gnomad4 EAS
AF:
0.635
Gnomad4 SAS
AF:
0.771
Gnomad4 FIN
AF:
0.752
Gnomad4 NFE
AF:
0.790
Gnomad4 OTH
AF:
0.734
Alfa
AF:
0.782
Hom.:
23021
Bravo
AF:
0.714
Asia WGS
AF:
0.686
AC:
2385
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
2.2
DANN
Benign
0.34

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.

Other links and lift over

dbSNP: rs261334; hg19: chr15-58726744; API