rs12591551

Positions:

• chr15-57989605-C-A
• chr15-57989605-C-T

Variant summary

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

The NM_003888.4(ALDH1A2):​c.798+3100G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 151,974 control chromosomes in the GnomAD database, including 587 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 0.087 (587 hom., cov: 32)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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 (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A2	NM_003888.4	c.798+3100G>T		intron_variant		ENST00000249750.9	NP_003879.2
ALDH1A2	NM_001206897.2	c.735+3100G>T		intron_variant			NP_001193826.1
ALDH1A2	NM_170696.3	c.684+3340G>T		intron_variant			NP_733797.1
ALDH1A2	NM_170697.3	c.510+3100G>T		intron_variant			NP_733798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.798+3100G>T		intron_variant		1	NM_003888.4	ENSP00000249750	P1

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13231 AN: 151856 Hom.: 584 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0871 AC: 13243 AN: 151974 Hom.: 587 Cov.: 32 AF XY: 0.0891 AC XY: 6619 AN XY: 74290

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0912

Gnomad4 ASJ AF: 0.0692

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.0905

Gnomad4 FIN AF: 0.0762

Gnomad4 NFE AF: 0.0751

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0237 Hom.: 14

Bravo AF: 0.0898

Asia WGS AF: 0.100 AC: 346 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	1.9
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12591551; hg19: chr15-58281803;