rs4646580

Positions:

• chr15-58037013-A-G

Variant summary

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

The NM_003888.4(ALDH1A2):​c.118-22732T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,372 control chromosomes in the GnomAD database, including 17,257 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 0.47 (17257 hom., cov: 31)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A2	NM_003888.4	c.118-22732T>C		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.54+20999T>C		intron_variant
ALDH1A2	NM_170696.3	c.118-22732T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.118-22732T>C		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71216 AN: 151254 Hom.: 17249 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.471 AC: 71255 AN: 151372 Hom.: 17257 Cov.: 31 AF XY: 0.467 AC XY: 34561 AN XY: 73938

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.450

Alfa AF: 0.503 Hom.: 8480

Bravo AF: 0.460

Asia WGS AF: 0.288 AC: 997 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.50

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: rs4646580; hg19: chr15-58329211;