rs4646830

Variant names:

• chr6-24494822-C-A
• rs4646830
• XM_017010753.3:c.44+145G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The XM_017010753.3(GPLD1):​c.44+145G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000177 in 564,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: GPLD1 XM_017010753.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

Genes affected

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]

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH5A1	NM_001080.3	c.-175C>A		upstream_gene_variant		ENST00000357578.8	NP_001071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH5A1	ENST00000357578.8	c.-175C>A		upstream_gene_variant		1	NM_001080.3	ENSP00000350191.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000177 AC: 1 AN: 564168 Hom.: 0 Cov.: 8 AF XY: 0.00000364 AC XY: 1 AN XY: 274806

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 12486

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 7108

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 10256

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 22700

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 8826

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 20366

Gnomad4 NFE exome AF: 0.00000220 AC: 1 AN: 454504

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 26070

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.6
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4646830; hg19: chr6-24495050;