rs1441815

Positions:

• chr15-57982031-C-A
• chr15-57982031-C-G

Variant summary

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

The NM_003888.4(ALDH1A2):​c.798+10674G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,026 control chromosomes in the GnomAD database, including 13,769 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 0.40 (13769 hom., cov: 32)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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 (SAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A2	NM_003888.4	c.798+10674G>T		intron_variant		ENST00000249750.9	NP_003879.2
ALDH1A2	NM_001206897.2	c.735+10674G>T		intron_variant			NP_001193826.1
ALDH1A2	NM_170696.3	c.684+10914G>T		intron_variant			NP_733797.1
ALDH1A2	NM_170697.3	c.510+10674G>T		intron_variant			NP_733798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.798+10674G>T		intron_variant		1	NM_003888.4	ENSP00000249750	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60640 AN: 151908 Hom.: 13759 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.399 AC: 60664 AN: 152026 Hom.: 13769 Cov.: 32 AF XY: 0.406 AC XY: 30175 AN XY: 74308

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.453

Alfa AF: 0.448 Hom.: 21525

Bravo AF: 0.394

Asia WGS AF: 0.685 AC: 2383 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	0.35
DANN	Benign	0.37

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: rs1441815; hg19: chr15-58274229;