rs2070895

Positions:

• chr15-58431740-G-A
• chr15-58431740-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000414170.7(LIPC):​c.-40-253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 447,094 control chromosomes in the GnomAD database, including 21,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9796 hom., cov: 32)
  • Exomes 𝑓: 0.26 (11482 hom.)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:2
• Conservation: PhyloP100: 0.453

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-58431740-G-A is Benign according to our data. Variant chr15-58431740-G-A is described in ClinVar as [Benign]. Clinvar id is 14454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000414170.7	c.-40-253G>A		intron_variant		1		ENSP00000395569
LIPC	ENST00000356113.10	c.-40-253G>A		intron_variant		2		ENSP00000348425	P1
ALDH1A2	ENST00000558239.5	c.-306-11635C>T		intron_variant		4		ENSP00000453292

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50467 AN: 151884 Hom.: 9765 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.260 AC: 76715 AN: 295092 Hom.: 11482 AF XY: 0.257 AC XY: 41006 AN XY: 159688

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.262

GnomAD4 genome AF: 0.332 AC: 50533 AN: 152002 Hom.: 9796 Cov.: 32 AF XY: 0.336 AC XY: 24986 AN XY: 74296

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.321

Alfa AF: 0.241 Hom.: 3372

Bravo AF: 0.355

Asia WGS AF: 0.371 AC: 1291 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 07, 2018	This variant is associated with the following publications: (PMID: 18364377, 20222961, 10894818) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Diabetes mellitus type 2, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jun 01, 2008

- -

High density lipoprotein cholesterol level quantitative trait locus 12 Other:1

association, no assertion criteria provided

literature only

OMIM

Jun 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.46

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: rs2070895; hg19: chr15-58723939;