rs633695

Variant names:

• chr15-58433640-A-G
• rs633695
• NM_000236.3:c.88+1520A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-58433640-A-G
• chr15-58433640-A-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+1520A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,060 control chromosomes in the GnomAD database, including 10,871 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 (10871 hom., cov: 32)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23
• Publications: 17 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.88+1520A>G		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.88+1520A>G		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55388 AN: 151942 Hom.: 10853 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.365 AC: 55443 AN: 152060 Hom.: 10871 Cov.: 32 AF XY: 0.369 AC XY: 27402 AN XY: 74346

African (AFR) AF: 0.430 AC: 17835 AN: 41464

American (AMR) AF: 0.462 AC: 7066 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1166 AN: 3452

East Asian (EAS) AF: 0.645 AC: 3330 AN: 5166

South Asian (SAS) AF: 0.389 AC: 1872 AN: 4818

European-Finnish (FIN) AF: 0.307 AC: 3254 AN: 10586

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19838 AN: 67976

Other (OTH) AF: 0.380 AC: 804 AN: 2116

Alfa AF: 0.322 Hom.: 26698

Bravo AF: 0.382

Asia WGS AF: 0.520 AC: 1807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.019
DANN	Benign	0.32
PhyloP100		-3.2
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: rs633695; hg19: chr15-58725839;