rs382086

chr15-58341448-A-Gchr15-58341448-A-T

Variant summary

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

The ENST00000558239.5(ALDH1A2):c.-172+78523T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,974 control chromosomes in the GnomAD database, including 32,201 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 0.65 (32201 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000558239.5	c.-172+78523T>C		intron_variant		4
ALDH1A2	ENST00000560863.5	n.415+78523T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98353 AN: 151856 Hom.: 32181 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.648 AC: 98424 AN: 151974 Hom.: 32201 Cov.: 32 AF XY: 0.643 AC XY: 47746 AN XY: 74304

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.655

Alfa AF: 0.668 Hom.: 55802

Bravo AF: 0.645

Asia WGS AF: 0.577 AC: 1997 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.9
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs382086; hg19: chr15-58633647;