rs8192701

chr15-58432172-C-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+52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,315,820 control chromosomes in the GnomAD database, including 13,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1074 hom., cov: 32)
  • Exomes 𝑓: 0.14 (12165 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.107

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=-0.61).
• BP6: Variant 15-58432172-C-T is Benign according to our data. Variant chr15-58432172-C-T is described in ClinVar as [Benign]. Clinvar id is 1244570.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-58432172-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPC	NM_000236.3	c.88+52C>T		intron_variant		ENST00000299022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPC	ENST00000299022.10	c.88+52C>T		intron_variant		1	NM_000236.3	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15794 AN: 152104 Hom.: 1075 Cov.: 32

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0776

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0573

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.0936

GnomAD3 exomes AF: 0.122 AC: 30468 AN: 249972 Hom.: 2169 AF XY: 0.129 AC XY: 17435 AN XY: 135196

Gnomad AFR exome AF: 0.0212

Gnomad AMR exome AF: 0.0601

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.0567

Gnomad SAS exome AF: 0.152

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.140 AC: 163205 AN: 1163598 Hom.: 12165 Cov.: 16 AF XY: 0.142 AC XY: 84048 AN XY: 593366

Gnomad4 AFR exome AF: 0.0228

Gnomad4 AMR exome AF: 0.0650

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0446

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.104 AC: 15783 AN: 152222 Hom.: 1074 Cov.: 32 AF XY: 0.105 AC XY: 7807 AN XY: 74410

Gnomad4 AFR AF: 0.0261

Gnomad4 AMR AF: 0.0774

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.0575

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.0921

Alfa AF: 0.134 Hom.: 777

Bravo AF: 0.0938

Asia WGS AF: 0.100 AC: 347 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

Sep 21, 2018

This variant is associated with the following publications: (PMID: 14551916) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	6.2
Dann	Benign	0.85

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: rs8192701; hg19: chr15-58724371;