rs8192701

Variant names:

• chr15-58432172-C-T
• rs8192701
• NM_000236.3:c.88+52C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.107
• Publications: 19 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 -20 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 VariationId is 1244570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.88+52C>T		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.88+52C>T		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5

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

GnomAD2 exomes AF: 0.122 AC: 30468 AN: 249972 AF XY: 0.129

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 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

African (AFR) AF: 0.0228 AC: 630 AN: 27672

American (AMR) AF: 0.0650 AC: 2879 AN: 44304

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3178 AN: 24178

East Asian (EAS) AF: 0.0446 AC: 1710 AN: 38370

South Asian (SAS) AF: 0.152 AC: 12221 AN: 80256

European-Finnish (FIN) AF: 0.167 AC: 8866 AN: 53206

Middle Eastern (MID) AF: 0.109 AC: 566 AN: 5206

European-Non Finnish (NFE) AF: 0.151 AC: 126719 AN: 839730

Other (OTH) AF: 0.127 AC: 6436 AN: 50676

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

African (AFR) AF: 0.0261 AC: 1086 AN: 41556

American (AMR) AF: 0.0774 AC: 1184 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3466

East Asian (EAS) AF: 0.0575 AC: 298 AN: 5186

South Asian (SAS) AF: 0.148 AC: 712 AN: 4818

European-Finnish (FIN) AF: 0.165 AC: 1744 AN: 10570

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9950 AN: 68020

Other (OTH) AF: 0.0921 AC: 194 AN: 2106

Alfa AF: 0.133 Hom.: 1065

Bravo AF: 0.0938

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.11
PromoterAI		-0.0026	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs8192701; hg19: chr15-58724371; COSMIC: COSV107334510; COSMIC: COSV107334510;