chr15-58431398-G-A

Variant names:

• chr15-58431398-G-A
• rs36041167
• ENST00000414170.7:c.-40-595G>A

Variant summary

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

The ENST00000414170.7(LIPC):​c.-40-595G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 518,692 control chromosomes in the GnomAD database, including 706 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 0.038 (157 hom., cov: 32)
  • Exomes 𝑓: 0.047 (549 hom.)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0559 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.-40-595G>A		intron_variant	Intron 1 of 9	1		ENSP00000395569.3
LIPC	ENST00000356113.10	c.-41+247G>A		intron_variant	Intron 2 of 10	2		ENSP00000348425.6
ALDH1A2	ENST00000558239.5	c.-306-11293C>T		intron_variant	Intron 1 of 3	4		ENSP00000453292.1

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5832 AN: 152130 Hom.: 157 Cov.: 32

Gnomad AFR AF: 0.00992

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0388

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0497

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0574

Gnomad OTH AF: 0.0502

GnomAD4 exome AF: 0.0471 AC: 17271 AN: 366444 Hom.: 549 AF XY: 0.0497 AC XY: 10442 AN XY: 210112

African (AFR) AF: 0.00943 AC: 99 AN: 10498

American (AMR) AF: 0.0198 AC: 719 AN: 36278

Ashkenazi Jewish (ASJ) AF: 0.0603 AC: 703 AN: 11666

East Asian (EAS) AF: 0.000228 AC: 3 AN: 13168

South Asian (SAS) AF: 0.0534 AC: 3564 AN: 66754

European-Finnish (FIN) AF: 0.0341 AC: 577 AN: 16914

Middle Eastern (MID) AF: 0.0912 AC: 260 AN: 2852

European-Non Finnish (NFE) AF: 0.0549 AC: 10533 AN: 191714

Other (OTH) AF: 0.0490 AC: 813 AN: 16600

GnomAD4 genome AF: 0.0383 AC: 5832 AN: 152248 Hom.: 157 Cov.: 32 AF XY: 0.0366 AC XY: 2721 AN XY: 74438

African (AFR) AF: 0.00989 AC: 411 AN: 41552

American (AMR) AF: 0.0387 AC: 592 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0500 AC: 241 AN: 4822

European-Finnish (FIN) AF: 0.0326 AC: 346 AN: 10604

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0574 AC: 3906 AN: 68014

Other (OTH) AF: 0.0497 AC: 105 AN: 2114

Alfa AF: 0.0535 Hom.: 163

Bravo AF: 0.0372

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.76
DANN	Benign	0.33
PhyloP100		-0.030
Mutation Taster		=100/0	polymorphism

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: rs36041167; hg19: chr15-58723597;