ENST00000414170.7:c.-40-766A>G

Variant names:

• chr15-58431227-A-G
• rs1077835
• ENST00000414170.7:c.-40-766A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000414170.7(LIPC):​c.-40-766A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 360,436 control chromosomes in the GnomAD database, including 18,253 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (10041 hom., cov: 31)
  • Exomes 𝑓: 0.26 (8212 hom.)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 50 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000414170.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000414170.7	TSL:1	c.-40-766A>G		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000356113.10	TSL:2	c.-41+76A>G		intron	N/A	ENSP00000348425.6
	ALDH1A2	ENST00000558239.5	TSL:4	c.-306-11122T>C		intron	N/A	ENSP00000453292.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51039 AN: 151866 Hom.: 10010 Cov.: 31

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.262 AC: 54557 AN: 208452 Hom.: 8212 AF XY: 0.258 AC XY: 29846 AN XY: 115538

African (AFR) AF: 0.527 AC: 2819 AN: 5354

American (AMR) AF: 0.495 AC: 5875 AN: 11862

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 1028 AN: 4756

East Asian (EAS) AF: 0.402 AC: 3396 AN: 8438

South Asian (SAS) AF: 0.256 AC: 10893 AN: 42592

European-Finnish (FIN) AF: 0.260 AC: 2303 AN: 8852

Middle Eastern (MID) AF: 0.194 AC: 153 AN: 788

European-Non Finnish (NFE) AF: 0.220 AC: 25505 AN: 115822

Other (OTH) AF: 0.259 AC: 2585 AN: 9988

GnomAD4 genome AF: 0.336 AC: 51105 AN: 151984 Hom.: 10041 Cov.: 31 AF XY: 0.340 AC XY: 25281 AN XY: 74314

African (AFR) AF: 0.516 AC: 21376 AN: 41398

American (AMR) AF: 0.433 AC: 6608 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3462

East Asian (EAS) AF: 0.417 AC: 2160 AN: 5174

South Asian (SAS) AF: 0.282 AC: 1357 AN: 4818

European-Finnish (FIN) AF: 0.276 AC: 2923 AN: 10582

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 14998 AN: 67958

Other (OTH) AF: 0.325 AC: 685 AN: 2110

Alfa AF: 0.280 Hom.: 11570

Bravo AF: 0.359

Asia WGS AF: 0.373 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.050
DANN	Benign	0.66
PhyloP100		-2.4
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: rs1077835; hg19: chr15-58723426;