chr6-24494822-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.07

Publications

9 publications found

Variant links:

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]

ALDH5A1 links:

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]

GPLD1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000859835.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
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.:

show subpopulations

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.:

AF XY:

0.349

AC XY:

95606

AN XY:

274040

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6172

12343

18515

24686

30858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5124

10248

15372

20496

25620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.337

AC:

51217

AN:

151998

Hom.:

8971

Cov.:

AF XY:

0.330

AC XY:

24486

AN XY:

74280

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.352

AC:

23876

AN:

67918

Other (OTH)

AF:

0.310

AC:

654

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1729

3458

5187

6916

8645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.7

(source)

DANN

Benign

0.57

PhyloP100

-1.1

PromoterAI

-0.070

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over