rs2099190

Variant names:

• chr15-58460691-C-A
• rs2099190
• NM_000236.3:c.88+28571C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-58460691-C-A
• chr15-58460691-C-G
• chr15-58460691-C-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+28571C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,068 control chromosomes in the GnomAD database, including 15,540 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 0.44 (15540 hom., cov: 32)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.922
• Publications: 3 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.88+28571C>A		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2
LIPC-AS1	NR_120338.1	n.209-23779G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.88+28571C>A		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67458 AN: 151950 Hom.: 15532 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.444 AC: 67491 AN: 152068 Hom.: 15540 Cov.: 32 AF XY: 0.449 AC XY: 33345 AN XY: 74340

African (AFR) AF: 0.323 AC: 13421 AN: 41506

American (AMR) AF: 0.396 AC: 6062 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1640 AN: 3468

East Asian (EAS) AF: 0.516 AC: 2655 AN: 5146

South Asian (SAS) AF: 0.527 AC: 2539 AN: 4822

European-Finnish (FIN) AF: 0.570 AC: 6010 AN: 10550

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33689 AN: 67970

Other (OTH) AF: 0.462 AC: 973 AN: 2108

Alfa AF: 0.442 Hom.: 13893

Bravo AF: 0.426

Asia WGS AF: 0.538 AC: 1867 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	3.2
DANN	Benign	0.37
PhyloP100		0.92
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: rs2099190; hg19: chr15-58752890;