rs493258

Positions:

• chr15-58395681-T-C

Variant summary

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

The ENST00000558239.5(ALDH1A2):​c.-172+24290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,130 control chromosomes in the GnomAD database, including 19,079 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 0.49 (19079 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.58395681T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000558239.5	c.-172+24290A>G		intron_variant		4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+24290A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75132 AN: 152012 Hom.: 19065 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.494 AC: 75200 AN: 152130 Hom.: 19079 Cov.: 32 AF XY: 0.490 AC XY: 36440 AN XY: 74348

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.511

Alfa AF: 0.527 Hom.: 37331

Bravo AF: 0.500

Asia WGS AF: 0.309 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs493258; hg19: chr15-58687880;