rs417344

Variant names:

• chr15-58425720-T-C
• rs417344
• ENST00000414170.7:c.-40-6273T>C

Variant summary

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

The ENST00000414170.7(LIPC):​c.-40-6273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,182 control chromosomes in the GnomAD database, including 1,521 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 0.14 (1521 hom., cov: 32)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• Publications: 7 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 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.-40-6273T>C		intron_variant	Intron 1 of 9	1		ENSP00000395569.3
LIPC	ENST00000356113.10	c.-365-5107T>C		intron_variant	Intron 1 of 10	2		ENSP00000348425.6
ALDH1A2	ENST00000558239.5	c.-306-5615A>G		intron_variant	Intron 1 of 3	4		ENSP00000453292.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20844 AN: 152064 Hom.: 1514 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0765

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.137 AC: 20872 AN: 152182 Hom.: 1521 Cov.: 32 AF XY: 0.137 AC XY: 10192 AN XY: 74402

African (AFR) AF: 0.122 AC: 5062 AN: 41520

American (AMR) AF: 0.0895 AC: 1368 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3472

East Asian (EAS) AF: 0.0766 AC: 397 AN: 5180

South Asian (SAS) AF: 0.145 AC: 696 AN: 4812

European-Finnish (FIN) AF: 0.172 AC: 1820 AN: 10576

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10654 AN: 68014

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.147 Hom.: 3661

Bravo AF: 0.130

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.4
DANN	Benign	0.87
PhyloP100		-0.16
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: rs417344; hg19: chr15-58717919;