rs10468017

Positions:

• chr15-58386313-C-T

Variant summary

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

The ENST00000558239.5(ALDH1A2):​c.-172+33658G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,102 control chromosomes in the GnomAD database, including 4,850 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 0.24 (4850 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

Genes affected

ALDH1A2 (HGNC:15472): (aldehyde dehydrogenase 1 family member A2) This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000558239.5	c.-172+33658G>A		intron_variant		4		ENSP00000453292
ALDH1A2	ENST00000560863.5	n.415+33658G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36702 AN: 151984 Hom.: 4847 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.241 AC: 36717 AN: 152102 Hom.: 4850 Cov.: 32 AF XY: 0.241 AC XY: 17950 AN XY: 74342

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.249

Alfa AF: 0.272 Hom.: 9066

Bravo AF: 0.228

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
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: rs10468017; hg19: chr15-58678512;