rs6493978

Positions:

• chr15-58033796-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.118-19515G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 148,950 control chromosomes in the GnomAD database, including 16,246 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 0.46 (16246 hom., cov: 26)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A2	NM_003888.4	c.118-19515G>A		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.55-19515G>A		intron_variant
ALDH1A2	NM_170696.3	c.118-19515G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.118-19515G>A		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 68689 AN: 148842 Hom.: 16238 Cov.: 26

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.461 AC: 68718 AN: 148950 Hom.: 16246 Cov.: 26 AF XY: 0.458 AC XY: 33224 AN XY: 72468

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.451

Alfa AF: 0.492 Hom.: 2321

Bravo AF: 0.452

Asia WGS AF: 0.286 AC: 989 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.099

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: rs6493978; hg19: chr15-58325994;