ENST00000414170.7:c.-40-713T>C

Variant names:

• chr15-58431280-T-C
• rs1077834
• ENST00000414170.7:c.-40-713T>C

Variant summary

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

The ENST00000414170.7(LIPC):​c.-40-713T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 381,066 control chromosomes in the GnomAD database, including 18,861 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 0.33 (9945 hom., cov: 31)
  • Exomes 𝑓: 0.26 (8916 hom.)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 61 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 = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000414170.7	c.-40-713T>C		intron_variant	Intron 1 of 9	1		ENSP00000395569.3
LIPC	ENST00000356113.10	c.-41+129T>C		intron_variant	Intron 2 of 10	2		ENSP00000348425.6
ALDH1A2	ENST00000558239.5	c.-306-11175A>G		intron_variant	Intron 1 of 3	4		ENSP00000453292.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50756 AN: 151822 Hom.: 9914 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.260 AC: 59481 AN: 229126 Hom.: 8916 AF XY: 0.255 AC XY: 32742 AN XY: 128378

African (AFR) AF: 0.517 AC: 3042 AN: 5882

American (AMR) AF: 0.502 AC: 7012 AN: 13974

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 1074 AN: 5896

East Asian (EAS) AF: 0.404 AC: 3539 AN: 8760

South Asian (SAS) AF: 0.252 AC: 11683 AN: 46374

European-Finnish (FIN) AF: 0.255 AC: 2595 AN: 10194

Middle Eastern (MID) AF: 0.204 AC: 395 AN: 1940

European-Non Finnish (NFE) AF: 0.218 AC: 27351 AN: 125210

Other (OTH) AF: 0.256 AC: 2790 AN: 10896

GnomAD4 genome AF: 0.334 AC: 50821 AN: 151940 Hom.: 9945 Cov.: 31 AF XY: 0.338 AC XY: 25140 AN XY: 74286

African (AFR) AF: 0.515 AC: 21312 AN: 41384

American (AMR) AF: 0.431 AC: 6583 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3462

East Asian (EAS) AF: 0.417 AC: 2152 AN: 5162

South Asian (SAS) AF: 0.280 AC: 1349 AN: 4816

European-Finnish (FIN) AF: 0.278 AC: 2930 AN: 10558

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14966 AN: 67966

Other (OTH) AF: 0.321 AC: 678 AN: 2110

Alfa AF: 0.272 Hom.: 13237

Bravo AF: 0.357

Asia WGS AF: 0.372 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.66
PhyloP100		-2.3
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: rs1077834; hg19: chr15-58723479; COSMIC: COSV54426479; COSMIC: COSV54426479;