chr15-58431388-G-T

Variant names:

• chr15-58431388-G-T
• rs35588604
• ENST00000414170.7:c.-40-605G>T

Variant summary

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

The ENST00000414170.7(LIPC):​c.-40-605G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 518,508 control chromosomes in the GnomAD database, including 672 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 0.051 (401 hom., cov: 31)
  • Exomes 𝑓: 0.028 (271 hom.)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 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.-40-605G>T		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000356113.10	TSL:2	c.-41+237G>T		intron	N/A	ENSP00000348425.6
	ALDH1A2	ENST00000558239.5	TSL:4	c.-306-11283C>A		intron	N/A	ENSP00000453292.1

Frequencies

GnomAD3 genomes AF: 0.0514 AC: 7825 AN: 152098 Hom.: 399 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0463

Gnomad ASJ AF: 0.0269

Gnomad EAS AF: 0.0641

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0484

GnomAD4 exome AF: 0.0277 AC: 10133 AN: 366292 Hom.: 271 AF XY: 0.0280 AC XY: 5884 AN XY: 210006

African (AFR) AF: 0.131 AC: 1369 AN: 10490

American (AMR) AF: 0.0391 AC: 1417 AN: 36238

Ashkenazi Jewish (ASJ) AF: 0.0305 AC: 355 AN: 11658

East Asian (EAS) AF: 0.0646 AC: 850 AN: 13168

South Asian (SAS) AF: 0.0429 AC: 2865 AN: 66722

European-Finnish (FIN) AF: 0.0244 AC: 413 AN: 16910

Middle Eastern (MID) AF: 0.0400 AC: 114 AN: 2848

European-Non Finnish (NFE) AF: 0.0118 AC: 2253 AN: 191660

Other (OTH) AF: 0.0299 AC: 497 AN: 16598

GnomAD4 genome AF: 0.0515 AC: 7836 AN: 152216 Hom.: 401 Cov.: 31 AF XY: 0.0524 AC XY: 3901 AN XY: 74430

African (AFR) AF: 0.126 AC: 5245 AN: 41500

American (AMR) AF: 0.0463 AC: 709 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0269 AC: 93 AN: 3462

East Asian (EAS) AF: 0.0641 AC: 332 AN: 5180

South Asian (SAS) AF: 0.0545 AC: 263 AN: 4824

European-Finnish (FIN) AF: 0.0300 AC: 318 AN: 10616

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 756 AN: 68018

Other (OTH) AF: 0.0479 AC: 101 AN: 2110

Alfa AF: 0.0433 Hom.: 120

Bravo AF: 0.0555

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.44
PhyloP100		0.48
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: rs35588604; hg19: chr15-58723587; COSMIC: COSV54426253; COSMIC: COSV54426253;