ENST00000414170.7:c.-40-2745A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000414170.7(LIPC):​c.-40-2745A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 141,412 control chromosomes in the GnomAD database, including 998 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 0.11 ( 998 hom., cov: 29)

Consequence

LIPC
ENST00000414170.7 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.934

Publications

5 publications found
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 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
LIPCENST00000414170.7 linkc.-40-2745A>G intron_variant Intron 1 of 9 1 ENSP00000395569.3 E7EUJ1
LIPCENST00000356113.10 linkc.-365-1579A>G intron_variant Intron 1 of 10 2 ENSP00000348425.6 P11150
ALDH1A2ENST00000558239.5 linkc.-306-9143T>C intron_variant Intron 1 of 3 4 ENSP00000453292.1 Q9UED3

Frequencies

GnomAD3 genomes
AF:
0.107
AC:
15145
AN:
141348
Hom.:
1000
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0285
Gnomad AMI
AF:
0.102
Gnomad AMR
AF:
0.0841
Gnomad ASJ
AF:
0.135
Gnomad EAS
AF:
0.0682
Gnomad SAS
AF:
0.155
Gnomad FIN
AF:
0.185
Gnomad MID
AF:
0.101
Gnomad NFE
AF:
0.143
Gnomad OTH
AF:
0.101
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.107
AC:
15134
AN:
141412
Hom.:
998
Cov.:
29
AF XY:
0.109
AC XY:
7462
AN XY:
68220
show subpopulations
African (AFR)
AF:
0.0285
AC:
1060
AN:
37242
American (AMR)
AF:
0.0839
AC:
1093
AN:
13020
Ashkenazi Jewish (ASJ)
AF:
0.135
AC:
460
AN:
3416
East Asian (EAS)
AF:
0.0683
AC:
316
AN:
4624
South Asian (SAS)
AF:
0.155
AC:
702
AN:
4518
European-Finnish (FIN)
AF:
0.185
AC:
1647
AN:
8910
Middle Eastern (MID)
AF:
0.0876
AC:
24
AN:
274
European-Non Finnish (NFE)
AF:
0.143
AC:
9547
AN:
66558
Other (OTH)
AF:
0.0993
AC:
194
AN:
1954
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
639
1278
1918
2557
3196
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
176
352
528
704
880
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.117
Hom.:
270
Bravo
AF:
0.0902
Asia WGS
AF:
0.100
AC:
347
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.54
DANN
Benign
0.58
PhyloP100
-0.93
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs12912415; hg19: chr15-58721447; API