rs473422

Variant names:

• chr15-58374142-C-T
• rs473422
• ENST00000558239.5:c.-172+45829G>A

Variant summary

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

The ENST00000558239.5(ALDH1A2):​c.-172+45829G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 151,962 control chromosomes in the GnomAD database, including 15,222 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 0.43 (15222 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• Publications: 10 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: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000558239.5	c.-172+45829G>A		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+45829G>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65516 AN: 151844 Hom.: 15188 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.432 AC: 65610 AN: 151962 Hom.: 15222 Cov.: 32 AF XY: 0.425 AC XY: 31595 AN XY: 74272

African (AFR) AF: 0.599 AC: 24834 AN: 41448

American (AMR) AF: 0.474 AC: 7237 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1277 AN: 3462

East Asian (EAS) AF: 0.225 AC: 1165 AN: 5178

South Asian (SAS) AF: 0.244 AC: 1172 AN: 4806

European-Finnish (FIN) AF: 0.290 AC: 3066 AN: 10556

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25534 AN: 67938

Other (OTH) AF: 0.444 AC: 937 AN: 2112

Alfa AF: 0.397 Hom.: 38466

Bravo AF: 0.452

Asia WGS AF: 0.265 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs473422; hg19: chr15-58666341;