rs2744601

chr6-24533277-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080.3(ALDH5A1):c.1403-230G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,142 control chromosomes in the GnomAD database, including 1,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1379 hom., cov: 32)
• Consequence: ALDH5A1 NM_001080.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.323

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-24533277-G-C is Benign according to our data. Variant chr6-24533277-G-C is described in ClinVar as [Benign]. Clinvar id is 1249324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH5A1	NM_001080.3	c.1403-230G>C		intron_variant		ENST00000357578.8
ALDH5A1	NM_001368954.1	c.1259-230G>C		intron_variant
ALDH5A1	NM_170740.1	c.1442-230G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH5A1	ENST00000357578.8	c.1403-230G>C		intron_variant		1	NM_001080.3	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19551 AN: 152022 Hom.: 1377 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.0665

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.129 AC: 19576 AN: 152142 Hom.: 1379 Cov.: 32 AF XY: 0.125 AC XY: 9272 AN XY: 74386

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0945

Gnomad4 ASJ AF: 0.0919

Gnomad4 EAS AF: 0.0667

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.117

Alfa AF: 0.141 Hom.: 225

Bravo AF: 0.124

Asia WGS AF: 0.0870 AC: 305 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.3
Dann	Benign	0.65

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: rs2744601; hg19: chr6-24533505;