rs4417206

Positions:

• chr10-95636713-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000371224.7(ALDH18A1):​c.558+380T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,172 control chromosomes in the GnomAD database, including 6,782 homozygotes. 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: 𝑓 0.28 (6782 hom., cov: 33)
• Consequence: ALDH18A1 ENST00000371224.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH18A1	NM_002860.4	c.558+380T>G		intron_variant		ENST00000371224.7	NP_002851.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH18A1	ENST00000371224.7	c.558+380T>G		intron_variant		1	NM_002860.4	ENSP00000360268	P3
ALDH18A1	ENST00000371221.3	c.558+380T>G		intron_variant		1		ENSP00000360265	A1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42091 AN: 152054 Hom.: 6790 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0441

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.276 AC: 42073 AN: 152172 Hom.: 6782 Cov.: 33 AF XY: 0.275 AC XY: 20447 AN XY: 74408

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0436

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.257

Alfa AF: 0.309 Hom.: 979

Bravo AF: 0.280

Asia WGS AF: 0.128 AC: 448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.9
DANN	Benign	0.91

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

Other links and lift over

dbSNP: rs4417206; hg19: chr10-97396470;