15-58454631-T-C

Variant names:

• chr15-58454631-T-C
• rs3825776
• NM_000236.3:c.88+22511T>C

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+22511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,078 control chromosomes in the GnomAD database, including 10,043 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 0.36 (10039 hom., cov: 33)
  • Exomes 𝑓: 0.42 (4 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 20 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]

ENSG00000277229 (HGNC:):

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 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+22511T>C		intron	N/A	NP_000227.2	P11150
	LIPC-AS1	NR_120338.1		n.209-17719A>G		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+22511T>C		intron	N/A	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.88+22511T>C		intron	N/A	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.130+22511T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54621 AN: 151912 Hom.: 10026 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.417 AC: 20 AN: 48 Hom.: 4 Cov.: 0 AF XY: 0.450 AC XY: 18 AN XY: 40

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.412 AC: 14 AN: 34

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.360 AC: 54670 AN: 152030 Hom.: 10039 Cov.: 33 AF XY: 0.361 AC XY: 26800 AN XY: 74298

African (AFR) AF: 0.382 AC: 15834 AN: 41464

American (AMR) AF: 0.452 AC: 6912 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1436 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2521 AN: 5148

South Asian (SAS) AF: 0.397 AC: 1914 AN: 4824

European-Finnish (FIN) AF: 0.281 AC: 2967 AN: 10570

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21878 AN: 67964

Other (OTH) AF: 0.371 AC: 783 AN: 2108

Alfa AF: 0.347 Hom.: 33961

Bravo AF: 0.376

Asia WGS AF: 0.408 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.4
DANN	Benign	0.73
PhyloP100		1.4
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: rs3825776; hg19: chr15-58746830;