rs2704188

chr15-58079484-G-A

Variant summary

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

The ENST00000558231.5(ALDH1A2):c.31-65203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,010 control chromosomes in the GnomAD database, including 33,160 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 0.64 (33160 hom., cov: 31)
• Consequence: ALDH1A2 ENST00000558231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 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	ENST00000557967.5	c.-172+58963C>T		intron_variant		4
ALDH1A2	ENST00000558231.5	c.31-65203C>T		intron_variant		2
ALDH1A2	ENST00000558239.5	c.-171-65203C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96858 AN: 151892 Hom.: 33112 Cov.: 31

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.638 AC: 96948 AN: 152010 Hom.: 33160 Cov.: 31 AF XY: 0.630 AC XY: 46784 AN XY: 74278

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.566

Alfa AF: 0.571 Hom.: 48556

Bravo AF: 0.638

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.19
Dann	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2704188; hg19: chr15-58371682;