rs10518978

Variant names:

• chr15-58463974-C-T
• rs10518978
• NM_000236.3:c.88+31854C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000236.3(LIPC):​c.88+31854C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,046 control chromosomes in the GnomAD database, including 1,511 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 0.14 (1511 hom., cov: 32)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.762
• Publications: 11 publications found

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]

LIPC-AS1 (HGNC:52294): (LIPC antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.88+31854C>T		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2
LIPC-AS1	NR_120338.1	n.209-27062G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.88+31854C>T		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21314 AN: 151928 Hom.: 1507 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.0827

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.129

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.140 AC: 21335 AN: 152046 Hom.: 1511 Cov.: 32 AF XY: 0.137 AC XY: 10181 AN XY: 74308

African (AFR) AF: 0.118 AC: 4908 AN: 41468

American (AMR) AF: 0.121 AC: 1851 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3466

East Asian (EAS) AF: 0.0961 AC: 498 AN: 5182

South Asian (SAS) AF: 0.0826 AC: 397 AN: 4808

European-Finnish (FIN) AF: 0.133 AC: 1403 AN: 10548

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11390 AN: 67990

Other (OTH) AF: 0.128 AC: 270 AN: 2114

Alfa AF: 0.161 Hom.: 1407

Bravo AF: 0.138

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.47
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10518978; hg19: chr15-58756173;