ENST00000558239.5:c.-172+20052T>A

Variant names:

• chr15-58399919-A-T
• rs397923
• ENST00000558239.5:c.-172+20052T>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+20052T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,202 control chromosomes in the GnomAD database, including 27,554 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 0.60 (27554 hom., cov: 34)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 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+20052T>A		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+20052T>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91268 AN: 152082 Hom.: 27530 Cov.: 34

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.600 AC: 91347 AN: 152202 Hom.: 27554 Cov.: 34 AF XY: 0.599 AC XY: 44550 AN XY: 74414

African (AFR) AF: 0.645 AC: 26790 AN: 41516

American (AMR) AF: 0.606 AC: 9275 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2026 AN: 3470

East Asian (EAS) AF: 0.606 AC: 3145 AN: 5186

South Asian (SAS) AF: 0.569 AC: 2745 AN: 4828

European-Finnish (FIN) AF: 0.537 AC: 5683 AN: 10588

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39731 AN: 67994

Other (OTH) AF: 0.602 AC: 1272 AN: 2114

Alfa AF: 0.605 Hom.: 3458

Bravo AF: 0.608

Asia WGS AF: 0.579 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs397923; hg19: chr15-58692118;