rs11858164

Variant names:

• chr15-58450532-T-G
• rs11858164
• NM_000236.3:c.88+18412T>G

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+18412T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,104 control chromosomes in the GnomAD database, including 14,863 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 0.39 (14863 hom., cov: 32)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 13 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.88+18412T>G		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2
LIPC-AS1	NR_120338.1	n.209-13620A>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.88+18412T>G		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59983 AN: 151986 Hom.: 14868 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.394 AC: 59967 AN: 152104 Hom.: 14863 Cov.: 32 AF XY: 0.391 AC XY: 29073 AN XY: 74342

African (AFR) AF: 0.106 AC: 4412 AN: 41528

American (AMR) AF: 0.372 AC: 5684 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1573 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1352 AN: 5180

South Asian (SAS) AF: 0.444 AC: 2140 AN: 4822

European-Finnish (FIN) AF: 0.519 AC: 5464 AN: 10536

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37652 AN: 67978

Other (OTH) AF: 0.418 AC: 883 AN: 2114

Alfa AF: 0.461 Hom.: 8576

Bravo AF: 0.369

Asia WGS AF: 0.307 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.7
DANN	Benign	0.63
PhyloP100		1.2
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: rs11858164; hg19: chr15-58742731;