rs7775073

chr6-24499323-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080.3(ALDH5A1):c.355-3200A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,874 control chromosomes in the GnomAD database, including 8,580 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 0.33 (8580 hom., cov: 30)
• Consequence: ALDH5A1 NM_001080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH5A1	NM_001080.3	c.355-3200A>G		intron_variant		ENST00000357578.8
ALDH5A1	NM_001368954.1	c.355-3200A>G		intron_variant
ALDH5A1	NM_170740.1	c.355-3200A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH5A1	ENST00000357578.8	c.355-3200A>G		intron_variant		1	NM_001080.3	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49900 AN: 151756 Hom.: 8564 Cov.: 30

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.298

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.329 AC: 49967 AN: 151874 Hom.: 8580 Cov.: 30 AF XY: 0.322 AC XY: 23908 AN XY: 74226

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.302

Alfa AF: 0.316 Hom.: 10649

Bravo AF: 0.324

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.5
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs7775073; hg19: chr6-24499551;