rs8034802

Variant names:

• chr15-58432593-T-A
• rs8034802
• NM_000236.3:c.88+473T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-58432593-T-A
• chr15-58432593-T-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+473T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,044 control chromosomes in the GnomAD database, including 9,218 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 0.34 (9218 hom., cov: 33)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534
• Publications: 25 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]

ALDH1A2 Gene-Disease associations (from GenCC):

• diaphragmatic hernia 4, with cardiovascular defects

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

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 (EAS) allele frequency at 95% confidence interval = 0.618 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+473T>A		intron	N/A	NP_000227.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.88+473T>A		intron	N/A	ENSP00000299022.5
	LIPC	ENST00000414170.7	TSL:1	c.88+473T>A		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000559845.5	TSL:1	n.130+473T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50934 AN: 151926 Hom.: 9205 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.335 AC: 50977 AN: 152044 Hom.: 9218 Cov.: 33 AF XY: 0.340 AC XY: 25302 AN XY: 74320

African (AFR) AF: 0.359 AC: 14880 AN: 41456

American (AMR) AF: 0.438 AC: 6686 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1050 AN: 3458

East Asian (EAS) AF: 0.636 AC: 3281 AN: 5156

South Asian (SAS) AF: 0.379 AC: 1824 AN: 4816

European-Finnish (FIN) AF: 0.305 AC: 3224 AN: 10566

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19033 AN: 68000

Other (OTH) AF: 0.347 AC: 732 AN: 2112

Alfa AF: 0.300 Hom.: 886

Bravo AF: 0.349

Asia WGS AF: 0.512 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		-0.53
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: rs8034802; hg19: chr15-58724792;