15-58388444-G-T

Variant names:

• chr15-58388444-G-T
• rs35853021
• ENST00000558239.5:c.-172+31527C>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+31527C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,544 control chromosomes in the GnomAD database, including 11,699 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 0.39 (11699 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 27 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A2	ENST00000558239.5	TSL:4	c.-172+31527C>A		intron	N/A	ENSP00000453292.1
	ALDH1A2	ENST00000560863.5	TSL:4	n.415+31527C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58366 AN: 151424 Hom.: 11686 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.386 AC: 58438 AN: 151544 Hom.: 11699 Cov.: 32 AF XY: 0.391 AC XY: 28945 AN XY: 74042

African (AFR) AF: 0.406 AC: 16761 AN: 41310

American (AMR) AF: 0.363 AC: 5534 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1147 AN: 3462

East Asian (EAS) AF: 0.782 AC: 3991 AN: 5106

South Asian (SAS) AF: 0.435 AC: 2090 AN: 4802

European-Finnish (FIN) AF: 0.404 AC: 4260 AN: 10534

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.345 AC: 23413 AN: 67766

Other (OTH) AF: 0.386 AC: 812 AN: 2106

Alfa AF: 0.368 Hom.: 28957

Bravo AF: 0.388

Asia WGS AF: 0.588 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.6
DANN	Benign	0.76
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs35853021; hg19: chr15-58680643;