chr15-58388444-G-T

Position:

• chr15-58388444-G-T

Variant summary

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

The ENST00000558239.5(ALDH1A2):​c.-172+31527C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,544 control chromosomes in the GnomAD database, including 11,699 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 0.39 (11699 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 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+31527C>A		intron_variant		4
ALDH1A2	ENST00000560863.5	n.415+31527C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58366 AN: 151424 Hom.: 11686 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.386 AC: 58438 AN: 151544 Hom.: 11699 Cov.: 32 AF XY: 0.391 AC XY: 28945 AN XY: 74042

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.782

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.386

Alfa AF: 0.362 Hom.: 7338

Bravo AF: 0.388

Asia WGS AF: 0.588 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.6
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35853021; hg19: chr15-58680643;