ENST00000558239.5:c.-172+82151C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000558239.5(ALDH1A2):​c.-172+82151C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 152,226 control chromosomes in the GnomAD database, including 103 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 0.036 ( 103 hom., cov: 33)

Consequence

ALDH1A2
ENST00000558239.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

Publications

8 publications found
Variant links:
Genes affected
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 -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 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
ALDH1A2ENST00000558239.5 linkc.-172+82151C>A intron_variant Intron 2 of 3 4 ENSP00000453292.1 Q9UED3
ALDH1A2ENST00000560863.5 linkn.415+82151C>A intron_variant Intron 3 of 4 4

Frequencies

GnomAD3 genomes
AF:
0.0355
AC:
5406
AN:
152108
Hom.:
103
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0590
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.0282
Gnomad ASJ
AF:
0.00577
Gnomad EAS
AF:
0.00365
Gnomad SAS
AF:
0.0154
Gnomad FIN
AF:
0.0313
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.0295
Gnomad OTH
AF:
0.0335
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0355
AC:
5405
AN:
152226
Hom.:
103
Cov.:
33
AF XY:
0.0348
AC XY:
2593
AN XY:
74412
show subpopulations
African (AFR)
AF:
0.0589
AC:
2444
AN:
41528
American (AMR)
AF:
0.0281
AC:
430
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.00577
AC:
20
AN:
3468
East Asian (EAS)
AF:
0.00366
AC:
19
AN:
5192
South Asian (SAS)
AF:
0.0154
AC:
74
AN:
4814
European-Finnish (FIN)
AF:
0.0313
AC:
332
AN:
10606
Middle Eastern (MID)
AF:
0.0170
AC:
5
AN:
294
European-Non Finnish (NFE)
AF:
0.0295
AC:
2009
AN:
68016
Other (OTH)
AF:
0.0331
AC:
70
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
275
550
824
1099
1374
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
60
120
180
240
300
<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:
0.0283
Hom.:
75
Bravo
AF:
0.0359
Asia WGS
AF:
0.0110
AC:
39
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.26
CADD
Benign
14
DANN
Benign
0.80
PhyloP100
1.2

Splicing

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

Publications

Other links and lift over

dbSNP: rs12910827; hg19: chr15-58630019; API