rs2744584

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001080.3(ALDH5A1):​c.726+141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 874,754 control chromosomes in the GnomAD database, including 30,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 5373 hom., cov: 33)
Exomes 𝑓: 0.25 ( 24779 hom. )

Consequence

ALDH5A1
NM_001080.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.694
Variant links:
Genes affected
ALDH5A1 (HGNC:408): (aldehyde dehydrogenase 5 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. This gene encodes a mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase. A deficiency of this enzyme, known as 4-hydroxybutyricaciduria, is a rare inborn error in the metabolism of the neurotransmitter 4-aminobutyric acid (GABA). In response to the defect, physiologic fluids from patients accumulate GHB, a compound with numerous neuromodulatory properties. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 6-24505126-G-A is Benign according to our data. Variant chr6-24505126-G-A is described in ClinVar as [Benign]. Clinvar id is 1237142.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ALDH5A1NM_001080.3 linkuse as main transcriptc.726+141G>A intron_variant ENST00000357578.8
ALDH5A1NM_001368954.1 linkuse as main transcriptc.726+141G>A intron_variant
ALDH5A1NM_170740.1 linkuse as main transcriptc.726+141G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ALDH5A1ENST00000357578.8 linkuse as main transcriptc.726+141G>A intron_variant 1 NM_001080.3 P1P51649-1

Frequencies

GnomAD3 genomes
AF:
0.260
AC:
39489
AN:
152008
Hom.:
5369
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.270
Gnomad AMI
AF:
0.386
Gnomad AMR
AF:
0.181
Gnomad ASJ
AF:
0.195
Gnomad EAS
AF:
0.100
Gnomad SAS
AF:
0.185
Gnomad FIN
AF:
0.301
Gnomad MID
AF:
0.140
Gnomad NFE
AF:
0.285
Gnomad OTH
AF:
0.234
GnomAD4 exome
AF:
0.250
AC:
180430
AN:
722626
Hom.:
24779
AF XY:
0.247
AC XY:
94149
AN XY:
381606
show subpopulations
Gnomad4 AFR exome
AF:
0.255
Gnomad4 AMR exome
AF:
0.165
Gnomad4 ASJ exome
AF:
0.185
Gnomad4 EAS exome
AF:
0.0770
Gnomad4 SAS exome
AF:
0.186
Gnomad4 FIN exome
AF:
0.306
Gnomad4 NFE exome
AF:
0.278
Gnomad4 OTH exome
AF:
0.246
GnomAD4 genome
AF:
0.260
AC:
39537
AN:
152128
Hom.:
5373
Cov.:
33
AF XY:
0.255
AC XY:
18925
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.271
Gnomad4 AMR
AF:
0.181
Gnomad4 ASJ
AF:
0.195
Gnomad4 EAS
AF:
0.101
Gnomad4 SAS
AF:
0.185
Gnomad4 FIN
AF:
0.301
Gnomad4 NFE
AF:
0.285
Gnomad4 OTH
AF:
0.232
Alfa
AF:
0.271
Hom.:
5255
Bravo
AF:
0.252
Asia WGS
AF:
0.146
AC:
511
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJul 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.35
DANN
Benign
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs2744584; hg19: chr6-24505354; API