rs2043085

Positions:

• chr15-58388755-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+31216A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,992 control chromosomes in the GnomAD database, including 22,876 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 0.54 (22876 hom., cov: 31)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 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+31216A>G		intron_variant		4		ENSP00000453292
ALDH1A2	ENST00000560863.5	n.415+31216A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81522 AN: 151874 Hom.: 22875 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.537 AC: 81554 AN: 151992 Hom.: 22876 Cov.: 31 AF XY: 0.534 AC XY: 39656 AN XY: 74278

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.564

Alfa AF: 0.610 Hom.: 35740

Bravo AF: 0.535

Asia WGS AF: 0.430 AC: 1496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2043085; hg19: chr15-58680954;