rs6494005

chr15-58432325-A-Gchr15-58432325-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000236.3(LIPC):c.88+205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 607,666 control chromosomes in the GnomAD database, including 67,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (13731 hom., cov: 33)
  • Exomes 𝑓: 0.47 (54121 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0810

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-58432325-A-G is Benign according to our data. Variant chr15-58432325-A-G is described in ClinVar as [Benign]. Clinvar id is 1264908.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-58432325-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPC	NM_000236.3	c.88+205A>G		intron_variant		ENST00000299022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPC	ENST00000299022.10	c.88+205A>G		intron_variant		1	NM_000236.3	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57570 AN: 152018 Hom.: 13731 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.474 AC: 216035 AN: 455530 Hom.: 54121 Cov.: 3 AF XY: 0.475 AC XY: 115248 AN XY: 242456

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.521

Gnomad4 EAS exome AF: 0.253

Gnomad4 SAS exome AF: 0.436

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.531

Gnomad4 OTH exome AF: 0.463

GnomAD4 genome AF: 0.378 AC: 57555 AN: 152136 Hom.: 13731 Cov.: 33 AF XY: 0.375 AC XY: 27879 AN XY: 74366

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.409

Alfa AF: 0.499 Hom.: 40103

Bravo AF: 0.357

Asia WGS AF: 0.289 AC: 1009 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.9
Dann	Benign	0.64

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: rs6494005; hg19: chr15-58724524;