ENST00000414170.7:c.-40-2745A>G

Variant names:

• chr15-58429248-A-G
• rs12912415
• ENST00000414170.7:c.-40-2745A>G

Variant summary

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

The ENST00000414170.7(LIPC):​c.-40-2745A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 141,412 control chromosomes in the GnomAD database, including 998 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 0.11 (998 hom., cov: 29)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000414170.7	c.-40-2745A>G		intron_variant	Intron 1 of 9	1		ENSP00000395569.3
LIPC	ENST00000356113.10	c.-365-1579A>G		intron_variant	Intron 1 of 10	2		ENSP00000348425.6
ALDH1A2	ENST00000558239.5	c.-306-9143T>C		intron_variant	Intron 1 of 3	4		ENSP00000453292.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 15145 AN: 141348 Hom.: 1000 Cov.: 29

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0682

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.107 AC: 15134 AN: 141412 Hom.: 998 Cov.: 29 AF XY: 0.109 AC XY: 7462 AN XY: 68220

African (AFR) AF: 0.0285 AC: 1060 AN: 37242

American (AMR) AF: 0.0839 AC: 1093 AN: 13020

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 460 AN: 3416

East Asian (EAS) AF: 0.0683 AC: 316 AN: 4624

South Asian (SAS) AF: 0.155 AC: 702 AN: 4518

European-Finnish (FIN) AF: 0.185 AC: 1647 AN: 8910

Middle Eastern (MID) AF: 0.0876 AC: 24 AN: 274

European-Non Finnish (NFE) AF: 0.143 AC: 9547 AN: 66558

Other (OTH) AF: 0.0993 AC: 194 AN: 1954

Alfa AF: 0.117 Hom.: 270

Bravo AF: 0.0902

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.54
DANN	Benign	0.58
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12912415; hg19: chr15-58721447;