ENST00000558239.5:c.-172+31216A>G

Variant names:

• chr15-58388755-T-C
• rs2043085
• ENST00000558239.5:c.-172+31216A>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+31216A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,992 control chromosomes in the GnomAD database, including 22,876 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 0.54 (22876 hom., cov: 31)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 83 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 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+31216A>G		intron	N/A	ENSP00000453292.1
	ALDH1A2	ENST00000560863.5	TSL:4	n.415+31216A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81522 AN: 151874 Hom.: 22875 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.537 AC: 81554 AN: 151992 Hom.: 22876 Cov.: 31 AF XY: 0.534 AC XY: 39656 AN XY: 74278

African (AFR) AF: 0.366 AC: 15176 AN: 41436

American (AMR) AF: 0.599 AC: 9156 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2165 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2640 AN: 5168

South Asian (SAS) AF: 0.467 AC: 2254 AN: 4824

European-Finnish (FIN) AF: 0.562 AC: 5937 AN: 10560

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42347 AN: 67942

Other (OTH) AF: 0.564 AC: 1188 AN: 2108

Alfa AF: 0.595 Hom.: 85186

Bravo AF: 0.535

Asia WGS AF: 0.430 AC: 1496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.81
PhyloP100		0.041

Splicing

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

Other links and lift over

dbSNP: rs2043085; hg19: chr15-58680954;