rs35511894

Variant names:

• chr15-58431510-C-T
• rs35511894
• ENST00000414170.7:c.-40-483C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000414170.7(LIPC):​c.-40-483C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00974 in 519,038 control chromosomes in the GnomAD database, including 52 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 0.0088 (13 hom., cov: 32)
  • Exomes 𝑓: 0.010 (39 hom.)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 4 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High Homozygotes in GnomAd4 at 13 AR,Unknown gene

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.-40-483C>T		intron_variant	Intron 1 of 9	1		ENSP00000395569.3
LIPC	ENST00000356113.10	c.-41+359C>T		intron_variant	Intron 2 of 10	2		ENSP00000348425.6
ALDH1A2	ENST00000558239.5	c.-306-11405G>A		intron_variant	Intron 1 of 3	4		ENSP00000453292.1

Frequencies

GnomAD3 genomes AF: 0.00883 AC: 1344 AN: 152174 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00937 AC: 2150 AN: 229354 AF XY: 0.00975

Gnomad AFR exome AF: 0.00272

Gnomad AMR exome AF: 0.00804

Gnomad ASJ exome AF: 0.0122

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00472

Gnomad NFE exome AF: 0.0147

Gnomad OTH exome AF: 0.0101

GnomAD4 exome AF: 0.0101 AC: 3710 AN: 366746 Hom.: 39 Cov.: 0 AF XY: 0.00983 AC XY: 2067 AN XY: 210284

African (AFR) AF: 0.00343 AC: 36 AN: 10510

American (AMR) AF: 0.00771 AC: 280 AN: 36296

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 147 AN: 11744

East Asian (EAS) AF: 0.00 AC: 0 AN: 13176

South Asian (SAS) AF: 0.00156 AC: 104 AN: 66766

European-Finnish (FIN) AF: 0.00526 AC: 89 AN: 16918

Middle Eastern (MID) AF: 0.00912 AC: 26 AN: 2852

European-Non Finnish (NFE) AF: 0.0147 AC: 2820 AN: 191872

Other (OTH) AF: 0.0125 AC: 208 AN: 16612

GnomAD4 genome AF: 0.00883 AC: 1344 AN: 152292 Hom.: 13 Cov.: 32 AF XY: 0.00831 AC XY: 619 AN XY: 74464

African (AFR) AF: 0.00262 AC: 109 AN: 41562

American (AMR) AF: 0.00981 AC: 150 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4822

European-Finnish (FIN) AF: 0.00424 AC: 45 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0138 AC: 939 AN: 68032

Other (OTH) AF: 0.0147 AC: 31 AN: 2116

Alfa AF: 0.0128 Hom.: 28

Bravo AF: 0.00942

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.0
DANN	Benign	0.73
PhyloP100		1.3
PromoterAI		-0.0055	Neutral
Mutation Taster		=100/0	polymorphism

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: rs35511894; hg19: chr15-58723709;