15-58459678-T-G

Variant names:

• chr15-58459678-T-G
• rs936960
• NM_000236.3:c.88+27558T>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+27558T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,284 control chromosomes in the GnomAD database, including 59,624 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 0.88 (59624 hom., cov: 34)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 10 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 (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	NM_000236.3	MANE Select	c.88+27558T>G		intron	N/A	NP_000227.2
	LIPC-AS1	NR_120338.1		n.209-22766A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.88+27558T>G		intron	N/A	ENSP00000299022.5
	LIPC	ENST00000414170.7	TSL:1	c.88+27558T>G		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000559845.5	TSL:1	n.130+27558T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134340 AN: 152168 Hom.: 59591 Cov.: 34

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.882

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

GnomAD4 genome AF: 0.883 AC: 134427 AN: 152284 Hom.: 59624 Cov.: 34 AF XY: 0.887 AC XY: 66072 AN XY: 74470

African (AFR) AF: 0.794 AC: 32990 AN: 41534

American (AMR) AF: 0.901 AC: 13795 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 3182 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5165 AN: 5174

South Asian (SAS) AF: 0.950 AC: 4589 AN: 4828

European-Finnish (FIN) AF: 0.953 AC: 10123 AN: 10620

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61560 AN: 68032

Other (OTH) AF: 0.883 AC: 1869 AN: 2116

Alfa AF: 0.883 Hom.: 39394

Bravo AF: 0.878

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.58
DANN	Benign	0.48
PhyloP100		-0.33
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: rs936960; hg19: chr15-58751877;