rs11188410

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002860.4(ALDH18A1):​c.558+289G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 152,276 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.059 ( 297 hom., cov: 33)

Consequence

ALDH18A1
NM_002860.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00300
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 10-95636804-C-A is Benign according to our data. Variant chr10-95636804-C-A is described in ClinVar as [Benign]. Clinvar id is 669715.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0816 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ALDH18A1NM_002860.4 linkuse as main transcriptc.558+289G>T intron_variant ENST00000371224.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ALDH18A1ENST00000371224.7 linkuse as main transcriptc.558+289G>T intron_variant 1 NM_002860.4 P3P54886-1
ALDH18A1ENST00000371221.3 linkuse as main transcriptc.558+289G>T intron_variant 1 A1P54886-2

Frequencies

GnomAD3 genomes
AF:
0.0594
AC:
9032
AN:
152158
Hom.:
298
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0478
Gnomad AMI
AF:
0.157
Gnomad AMR
AF:
0.0578
Gnomad ASJ
AF:
0.0230
Gnomad EAS
AF:
0.0446
Gnomad SAS
AF:
0.0891
Gnomad FIN
AF:
0.0764
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0641
Gnomad OTH
AF:
0.0521
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0593
AC:
9034
AN:
152276
Hom.:
297
Cov.:
33
AF XY:
0.0601
AC XY:
4476
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0477
Gnomad4 AMR
AF:
0.0578
Gnomad4 ASJ
AF:
0.0230
Gnomad4 EAS
AF:
0.0449
Gnomad4 SAS
AF:
0.0885
Gnomad4 FIN
AF:
0.0764
Gnomad4 NFE
AF:
0.0641
Gnomad4 OTH
AF:
0.0516
Alfa
AF:
0.0553
Hom.:
232
Bravo
AF:
0.0560
Asia WGS
AF:
0.0590
AC:
206
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.83
DANN
Benign
0.47

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11188410; hg19: chr10-97396561; API