rs493258

Variant names:

• chr15-58395681-T-C
• rs493258
• ENST00000558239.5:c.-172+24290A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000558239.5(ALDH1A2):​c.-172+24290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,130 control chromosomes in the GnomAD database, including 19,079 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 0.49 (19079 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 63 publications found

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]

ALDH1A2 Gene-Disease associations (from GenCC):

• diaphragmatic hernia 4, with cardiovascular defects

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558239.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A2	ENST00000558239.5	TSL:4	c.-172+24290A>G		intron	N/A	ENSP00000453292.1	Q9UED3
	ALDH1A2	ENST00000560863.5	TSL:4	n.415+24290A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75132 AN: 152012 Hom.: 19065 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.494 AC: 75200 AN: 152130 Hom.: 19079 Cov.: 32 AF XY: 0.490 AC XY: 36440 AN XY: 74348

African (AFR) AF: 0.448 AC: 18581 AN: 41488

American (AMR) AF: 0.541 AC: 8257 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1990 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1267 AN: 5182

South Asian (SAS) AF: 0.346 AC: 1668 AN: 4822

European-Finnish (FIN) AF: 0.486 AC: 5131 AN: 10564

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36644 AN: 68010

Other (OTH) AF: 0.511 AC: 1081 AN: 2114

Alfa AF: 0.522 Hom.: 76978

Bravo AF: 0.500

Asia WGS AF: 0.309 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs493258; hg19: chr15-58687880;