rs10882640

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002860.4(ALDH18A1):c.2206+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,612,192 control chromosomes in the GnomAD database, including 174,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12959 hom., cov: 31)

Exomes 𝑓: 0.46 ( 161480 hom. )

Consequence

ALDH18A1
NM_002860.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.231

Variant links:

Genes affected

ALDH18A1 (HGNC:9722): (aldehyde dehydrogenase 18 family member A1) This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. [provided by RefSeq, Jul 2008]

ALDH18A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 10-95610182-C-T is Benign according to our data. Variant chr10-95610182-C-T is described in ClinVar as [Benign]. Clinvar id is 258825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-95610182-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH18A1	NM_002860.4 link	c.2206+15G>A		intron_variant	Intron 17 of 17	ENST00000371224.7	NP_002851.2	P54886-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH18A1	ENST00000371224.7 link	c.2206+15G>A		intron_variant	Intron 17 of 17	1	NM_002860.4	ENSP00000360268.2		P54886-1
ALDH18A1	ENST00000371221.3 link	c.2200+15G>A		intron_variant	Intron 17 of 17	1		ENSP00000360265.3		P54886-2

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58801

AN:

151956

Hom.:

12971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.442

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.0844

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.392

GnomAD2 exomes

AF:

0.419

AC:

105115

AN:

250954

AF XY:

0.416

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.536

Gnomad ASJ exome

AF:

0.428

Gnomad EAS exome

AF:

0.0855

Gnomad FIN exome

AF:

0.472

Gnomad NFE exome

AF:

0.487

Gnomad OTH exome

AF:

0.444

GnomAD4 exome

AF:

0.461

AC:

672796

AN:

1460118

Hom.:

161480

Cov.:

AF XY:

0.456

AC XY:

331467

AN XY:

726422

show subpopulations

African (AFR)

AF:

0.187

AC:

6269

AN:

33450

American (AMR)

AF:

0.534

AC:

23840

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

10929

AN:

26114

East Asian (EAS)

AF:

0.0872

AC:

3457

AN:

39646

South Asian (SAS)

AF:

0.310

AC:

26746

AN:

86212

European-Finnish (FIN)

AF:

0.477

AC:

25442

AN:

53324

Middle Eastern (MID)

AF:

0.409

AC:

2351

AN:

5750

European-Non Finnish (NFE)

AF:

0.493

AC:

547545

AN:

1110616

Other (OTH)

AF:

0.435

AC:

26217

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

16902

33805

50707

67610

84512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.387

AC:

58780

AN:

152074

Hom.:

12959

Cov.:

AF XY:

0.385

AC XY:

28588

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.200

AC:

8320

AN:

41498

American (AMR)

AF:

0.498

AC:

7597

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1481

AN:

3472

East Asian (EAS)

AF:

0.0842

AC:

436

AN:

5176

South Asian (SAS)

AF:

0.290

AC:

1396

AN:

4814

European-Finnish (FIN)

AF:

0.472

AC:

4993

AN:

10578

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.489

AC:

33205

AN:

67952

Other (OTH)

AF:

0.388

AC:

819

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1726

3453

5179

6906

8632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.456

Hom.:

16721

Bravo

AF:

0.385

Asia WGS

AF:

0.173

AC:

607

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

ALDH18A1-related de Barsy syndrome

Benign:4

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 06, 2016

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 29, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Cutis laxa, autosomal dominant 3

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive complex spastic paraplegia type 9B

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary spastic paraplegia 9A

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

de Barsy syndrome;C1832669:Autosomal dominant spastic paraplegia type 9;C4225268:Cutis laxa, autosomal dominant 3

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.5

(source)

DANN

Benign

0.53

PhyloP100

-0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs10882640

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over