chr15-58382470-T-G

Variant names:

• chr15-58382470-T-G
• rs539901
• ENST00000558239.5:c.-172+37501A>C

Variant summary

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

The ENST00000558239.5(ALDH1A2):​c.-172+37501A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 152,256 control chromosomes in the GnomAD database, including 187 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 0.031 (187 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0861 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+37501A>C		intron	N/A	ENSP00000453292.1	Q9UED3
	ALDH1A2	ENST00000560863.5	TSL:4	n.415+37501A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4758 AN: 152138 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0289

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.0933

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00274

Gnomad OTH AF: 0.0349

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

GnomAD4 genome AF: 0.0314 AC: 4776 AN: 152256 Hom.: 187 Cov.: 32 AF XY: 0.0320 AC XY: 2381 AN XY: 74450

African (AFR) AF: 0.0776 AC: 3221 AN: 41534

American (AMR) AF: 0.0288 AC: 440 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 139 AN: 3466

East Asian (EAS) AF: 0.0930 AC: 482 AN: 5184

South Asian (SAS) AF: 0.0451 AC: 218 AN: 4830

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10626

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00274 AC: 186 AN: 67998

Other (OTH) AF: 0.0364 AC: 77 AN: 2116

Alfa AF: 0.0157 Hom.: 149

Bravo AF: 0.0356

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.64
PhyloP100		0.026

Splicing

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

Other links and lift over

dbSNP: rs539901; hg19: chr15-58674669;