rs2143083

Positions:

• chr6-24506826-T-C

Variant summary

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

The NM_001080.3(ALDH5A1):​c.726+1841T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 146,362 control chromosomes in the GnomAD database, including 28,077 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 0.63 (28077 hom., cov: 32)
• Consequence: ALDH5A1 NM_001080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH5A1	NM_001080.3	c.726+1841T>C		intron_variant		ENST00000357578.8	NP_001071.1
ALDH5A1	NM_001368954.1	c.726+1841T>C		intron_variant			NP_001355883.1
ALDH5A1	NM_170740.1	c.726+1841T>C		intron_variant			NP_733936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH5A1	ENST00000357578.8	c.726+1841T>C		intron_variant		1	NM_001080.3	ENSP00000350191	P1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 91669 AN: 146246 Hom.: 28071 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.627 AC: 91705 AN: 146362 Hom.: 28077 Cov.: 32 AF XY: 0.624 AC XY: 44574 AN XY: 71488

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.650

Alfa AF: 0.600 Hom.: 4490

Bravo AF: 0.606

Asia WGS AF: 0.468 AC: 1625 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.84

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: rs2143083; hg19: chr6-24507054;