15-58420004-T-G

Variant names:

• chr15-58420004-T-G
• rs11857380
• ENST00000414170.7:c.-41+9186T>G

Variant summary

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

The ENST00000414170.7(LIPC):​c.-41+9186T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,310 control chromosomes in the GnomAD database, including 2,681 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 0.18 (2679 hom., cov: 32)
  • Exomes 𝑓: 0.20 (2 hom.)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 16 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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 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.-41+9186T>G		intron_variant	Intron 1 of 9	1		ENSP00000395569.3
ALDH1A2	ENST00000560863.5	n.382A>C		non_coding_transcript_exon_variant	Exon 3 of 5	4
ALDH1A2	ENST00000558239.5	c.-205A>C		5_prime_UTR_variant	Exon 2 of 4	4		ENSP00000453292.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26916 AN: 152090 Hom.: 2675 Cov.: 32

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.196 AC: 20 AN: 102 Hom.: 2 Cov.: 0 AF XY: 0.197 AC XY: 15 AN XY: 76

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.171 AC: 14 AN: 82

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.177 AC: 26918 AN: 152208 Hom.: 2679 Cov.: 32 AF XY: 0.177 AC XY: 13199 AN XY: 74426

African (AFR) AF: 0.0926 AC: 3846 AN: 41546

American (AMR) AF: 0.187 AC: 2862 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 651 AN: 3466

East Asian (EAS) AF: 0.139 AC: 723 AN: 5192

South Asian (SAS) AF: 0.234 AC: 1127 AN: 4826

European-Finnish (FIN) AF: 0.237 AC: 2512 AN: 10580

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14471 AN: 67996

Other (OTH) AF: 0.202 AC: 427 AN: 2112

Alfa AF: 0.198 Hom.: 12136

Bravo AF: 0.168

Asia WGS AF: 0.170 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.8
DANN	Benign	0.82
PhyloP100		0.33
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: rs11857380; hg19: chr15-58712203;