rs4646830

Variant names:

• chr6-24494822-C-G
• rs4646830
• ENST00000859835.1:c.-175C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-24494822-C-G
• chr6-24494822-C-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000859835.1(ALDH5A1):​c.-175C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 714,560 control chromosomes in the GnomAD database, including 44,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (8971 hom., cov: 32)
  • Exomes 𝑓: 0.35 (35565 hom.)
• Consequence: ALDH5A1 ENST00000859835.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.07
• Publications: 9 publications found

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]

GPLD1 (HGNC:4459): (glycosylphosphatidylinositol specific phospholipase D1) Many proteins are tethered to the extracellular face of eukaryotic plasma membranes by a glycosylphosphatidylinositol (GPI) anchor. The GPI-anchor is a glycolipid found on many blood cells. The protein encoded by this gene is a GPI degrading enzyme. Glycosylphosphatidylinositol specific phospholipase D1 hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby releasing the attached protein from the plasma membrane. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 6-24494822-C-G is Benign according to our data. Variant chr6-24494822-C-G is described in ClinVar as Benign. ClinVar VariationId is 1282291.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000859835.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH5A1	NM_001080.3	MANE Select	c.-175C>G		upstream_gene	N/A	NP_001071.1	X5DQN2
	ALDH5A1	NM_170740.1		c.-175C>G		upstream_gene	N/A	NP_733936.1	X5D299
	ALDH5A1	NM_001368954.1		c.-175C>G		upstream_gene	N/A	NP_001355883.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH5A1	ENST00000859835.1		c.-175C>G		5_prime_UTR	Exon 1 of 10	ENSP00000529894.1
	ALDH5A1	ENST00000859836.1		c.-175C>G		5_prime_UTR	Exon 1 of 9	ENSP00000529895.1
	GPLD1	ENST00000474784.5	TSL:5	n.239+145G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51153 AN: 151880 Hom.: 8957 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.350 AC: 196995 AN: 562562 Hom.: 35565 Cov.: 8 AF XY: 0.349 AC XY: 95606 AN XY: 274040

African (AFR) AF: 0.376 AC: 4693 AN: 12466

American (AMR) AF: 0.230 AC: 1635 AN: 7094

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 2931 AN: 10240

East Asian (EAS) AF: 0.200 AC: 4527 AN: 22676

South Asian (SAS) AF: 0.290 AC: 2551 AN: 8804

European-Finnish (FIN) AF: 0.339 AC: 6884 AN: 20334

Middle Eastern (MID) AF: 0.229 AC: 425 AN: 1852

European-Non Finnish (NFE) AF: 0.363 AC: 164665 AN: 453088

Other (OTH) AF: 0.334 AC: 8684 AN: 26008

GnomAD4 genome AF: 0.337 AC: 51217 AN: 151998 Hom.: 8971 Cov.: 32 AF XY: 0.330 AC XY: 24486 AN XY: 74280

African (AFR) AF: 0.380 AC: 15782 AN: 41490

American (AMR) AF: 0.232 AC: 3546 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1018 AN: 3470

East Asian (EAS) AF: 0.194 AC: 998 AN: 5146

South Asian (SAS) AF: 0.285 AC: 1373 AN: 4812

European-Finnish (FIN) AF: 0.332 AC: 3506 AN: 10564

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.352 AC: 23876 AN: 67918

Other (OTH) AF: 0.310 AC: 654 AN: 2110

Alfa AF: 0.352 Hom.: 1169

Bravo AF: 0.332

Asia WGS AF: 0.256 AC: 894 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.7
DANN	Benign	0.57
PhyloP100		-1.1
PromoterAI		-0.070	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs4646830; hg19: chr6-24495050;