15-58438440-C-G

Variant names:

• chr15-58438440-C-G
• rs17301739
• NM_000236.3:c.88+6320C>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+6320C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 152,142 control chromosomes in the GnomAD database, including 336 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 0.066 (336 hom., cov: 32)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0838 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	NM_000236.3	MANE Select	c.88+6320C>G		intron	N/A	NP_000227.2	P11150
	LIPC-AS1	NR_120338.1		n.209-1528G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.88+6320C>G		intron	N/A	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.88+6320C>G		intron	N/A	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.130+6320C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0658 AC: 10006 AN: 152024 Hom.: 337 Cov.: 32

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0904

Gnomad SAS AF: 0.0820

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.0731

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

GnomAD4 genome AF: 0.0658 AC: 10013 AN: 152142 Hom.: 336 Cov.: 32 AF XY: 0.0654 AC XY: 4864 AN XY: 74398

African (AFR) AF: 0.0588 AC: 2443 AN: 41530

American (AMR) AF: 0.0429 AC: 657 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 448 AN: 3408

East Asian (EAS) AF: 0.0906 AC: 468 AN: 5164

South Asian (SAS) AF: 0.0821 AC: 396 AN: 4824

European-Finnish (FIN) AF: 0.0582 AC: 618 AN: 10618

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0693 AC: 4708 AN: 67976

Other (OTH) AF: 0.0780 AC: 165 AN: 2116

Alfa AF: 0.0290 Hom.: 11

Bravo AF: 0.0638

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
DANN	Benign	0.47
PhyloP100		0.27
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: rs17301739; hg19: chr15-58730639;