15-58432184-A-G

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+64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 1,220,094 control chromosomes in the GnomAD database, including 1,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (453 hom., cov: 32)
  • Exomes 𝑓: 0.021 (610 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.183

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=-0.64).
• BP6: Variant 15-58432184-A-G is Benign according to our data. Variant chr15-58432184-A-G is described in ClinVar as [Benign]. Clinvar id is 1243737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPC	NM_000236.3	c.88+64A>G		intron_variant		ENST00000299022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPC	ENST00000299022.10	c.88+64A>G		intron_variant		1	NM_000236.3	P1

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 8312 AN: 152178 Hom.: 450 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0501

GnomAD4 exome AF: 0.0207 AC: 22078 AN: 1067798 Hom.: 610 Cov.: 14 AF XY: 0.0211 AC XY: 11620 AN XY: 549612

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.0408

Gnomad4 ASJ exome AF: 0.0301

Gnomad4 EAS exome AF: 0.0591

Gnomad4 SAS exome AF: 0.0438

Gnomad4 FIN exome AF: 0.0248

Gnomad4 NFE exome AF: 0.00964

Gnomad4 OTH exome AF: 0.0301

GnomAD4 genome AF: 0.0547 AC: 8324 AN: 152296 Hom.: 453 Cov.: 32 AF XY: 0.0556 AC XY: 4143 AN XY: 74482

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0472

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.0638

Gnomad4 SAS AF: 0.0551

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0496

Alfa AF: 0.0201 Hom.: 145

Bravo AF: 0.0591

Asia WGS AF: 0.0570 AC: 201 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

Nov 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	5.9
Dann	Benign	0.77

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: rs11631342; hg19: chr15-58724383; COSMIC: COSV54427924; COSMIC: COSV54427924;