ENST00000414170.7:c.-40-517C>T

Variant names:

• chr15-58431476-C-T
• rs1800588
• ENST00000414170.7:c.-40-517C>T

Variant summary

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

The ENST00000414170.7(LIPC):​c.-40-517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 518,670 control chromosomes in the GnomAD database, including 26,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.33 (9579 hom., cov: 31)
  • Exomes 𝑓: 0.27 (16528 hom.)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 1.04
• Publications: 383 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 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.-40-517C>T		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000356113.10	TSL:2	c.-41+325C>T		intron	N/A	ENSP00000348425.6
	ALDH1A2	ENST00000558239.5	TSL:4	c.-306-11371G>A		intron	N/A	ENSP00000453292.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49690 AN: 151838 Hom.: 9546 Cov.: 31

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.322

GnomAD2 exomes AF: 0.303 AC: 69477 AN: 229344 AF XY: 0.284

Gnomad AFR exome AF: 0.507

Gnomad AMR exome AF: 0.563

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.378

Gnomad FIN exome AF: 0.252

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.272 AC: 99670 AN: 366714 Hom.: 16528 Cov.: 0 AF XY: 0.260 AC XY: 54624 AN XY: 210268

African (AFR) AF: 0.506 AC: 5315 AN: 10510

American (AMR) AF: 0.563 AC: 20450 AN: 36298

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 2208 AN: 11742

East Asian (EAS) AF: 0.392 AC: 5162 AN: 13170

South Asian (SAS) AF: 0.241 AC: 16115 AN: 66766

European-Finnish (FIN) AF: 0.248 AC: 4194 AN: 16918

Middle Eastern (MID) AF: 0.198 AC: 566 AN: 2852

European-Non Finnish (NFE) AF: 0.216 AC: 41413 AN: 191850

Other (OTH) AF: 0.256 AC: 4247 AN: 16608

GnomAD4 genome AF: 0.327 AC: 49760 AN: 151956 Hom.: 9579 Cov.: 31 AF XY: 0.331 AC XY: 24596 AN XY: 74292

African (AFR) AF: 0.506 AC: 20966 AN: 41410

American (AMR) AF: 0.425 AC: 6489 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3460

East Asian (EAS) AF: 0.399 AC: 2063 AN: 5170

South Asian (SAS) AF: 0.265 AC: 1275 AN: 4814

European-Finnish (FIN) AF: 0.269 AC: 2835 AN: 10558

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14624 AN: 67966

Other (OTH) AF: 0.318 AC: 669 AN: 2104

Alfa AF: 0.251 Hom.: 23789

Bravo AF: 0.350

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

High density lipoprotein cholesterol level quantitative trait locus 12 Other:1

Aug 01, 2004

OMIM

Significance: association

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.50
PhyloP100		1.0
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: rs1800588; hg19: chr15-58723675; COSMIC: COSV54424806; COSMIC: COSV54424806;