rs348457

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000689.5(ALDH1A1):​c.1035+1282G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,958 control chromosomes in the GnomAD database, including 14,273 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 0.43 ( 14273 hom., cov: 32)

Consequence

ALDH1A1
NM_000689.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0540
Variant links:
Genes affected
ALDH1A1 (HGNC:402): (aldehyde dehydrogenase 1 family member A1) The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet. [provided by RefSeq, Mar 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ALDH1A1NM_000689.5 linkuse as main transcriptc.1035+1282G>C intron_variant ENST00000297785.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ALDH1A1ENST00000297785.8 linkuse as main transcriptc.1035+1282G>C intron_variant 1 NM_000689.5 P1

Frequencies

GnomAD3 genomes
AF:
0.433
AC:
65710
AN:
151840
Hom.:
14276
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.423
Gnomad AMI
AF:
0.417
Gnomad AMR
AF:
0.445
Gnomad ASJ
AF:
0.368
Gnomad EAS
AF:
0.520
Gnomad SAS
AF:
0.352
Gnomad FIN
AF:
0.413
Gnomad MID
AF:
0.478
Gnomad NFE
AF:
0.441
Gnomad OTH
AF:
0.443
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.433
AC:
65723
AN:
151958
Hom.:
14273
Cov.:
32
AF XY:
0.429
AC XY:
31851
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.423
Gnomad4 AMR
AF:
0.444
Gnomad4 ASJ
AF:
0.368
Gnomad4 EAS
AF:
0.520
Gnomad4 SAS
AF:
0.350
Gnomad4 FIN
AF:
0.413
Gnomad4 NFE
AF:
0.441
Gnomad4 OTH
AF:
0.446
Alfa
AF:
0.441
Hom.:
1849
Bravo
AF:
0.439
Asia WGS
AF:
0.468
AC:
1627
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
2.9
DANN
Benign
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs348457; hg19: chr9-75530554; API