chr15-58427542-G-A

Variant names:

• chr15-58427542-G-A
• rs11635491
• ENST00000414170.7:c.-40-4451G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000414170.7(LIPC):​c.-40-4451G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,328 control chromosomes in the GnomAD database, including 5,648 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 0.27 (5648 hom., cov: 30)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000414170.7. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000414170.7	TSL:1	c.-40-4451G>A		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000356113.10	TSL:2	c.-365-3285G>A		intron	N/A	ENSP00000348425.6
	ALDH1A2	ENST00000558239.5	TSL:4	c.-306-7437C>T		intron	N/A	ENSP00000453292.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40585 AN: 151226 Hom.: 5635 Cov.: 30

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.268 AC: 40622 AN: 151328 Hom.: 5648 Cov.: 30 AF XY: 0.270 AC XY: 19927 AN XY: 73846

African (AFR) AF: 0.219 AC: 9021 AN: 41206

American (AMR) AF: 0.355 AC: 5387 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3462

East Asian (EAS) AF: 0.370 AC: 1899 AN: 5134

South Asian (SAS) AF: 0.268 AC: 1285 AN: 4800

European-Finnish (FIN) AF: 0.274 AC: 2847 AN: 10380

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.271 AC: 18411 AN: 67860

Other (OTH) AF: 0.288 AC: 602 AN: 2092

Alfa AF: 0.274 Hom.: 10389

Bravo AF: 0.276

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.66
PhyloP100		0.13
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: rs11635491; hg19: chr15-58719741;