rs1077835

chr15-58431227-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000414170.7(LIPC):c.-40-766A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 360,436 control chromosomes in the GnomAD database, including 18,253 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 0.34 (10041 hom., cov: 31)
  • Exomes 𝑓: 0.26 (8212 hom.)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPC	ENST00000414170.7	c.-40-766A>G		intron_variant		1
LIPC	ENST00000356113.10	c.-41+76A>G		intron_variant		2		P1
ALDH1A2	ENST00000558239.5	c.-306-11122T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51039 AN: 151866 Hom.: 10010 Cov.: 31

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.262 AC: 54557 AN: 208452 Hom.: 8212 AF XY: 0.258 AC XY: 29846 AN XY: 115538

Gnomad4 AFR exome AF: 0.527

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.402

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.336 AC: 51105 AN: 151984 Hom.: 10041 Cov.: 31 AF XY: 0.340 AC XY: 25281 AN XY: 74314

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.325

Alfa AF: 0.287 Hom.: 1231

Bravo AF: 0.359

Asia WGS AF: 0.373 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.050
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs1077835; hg19: chr15-58723426;