15-58331326-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000558239.5(ALDH1A2):c.-172+88645A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,810 control chromosomes in the GnomAD database, including 13,143 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 0.41 (13142 hom., cov: 29)
  • Exomes 𝑓: 0.40 (1 hom.)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000558239.5	c.-172+88645A>G		intron_variant		4
ALDH1A2	ENST00000558603.5	n.54A>G		non_coding_transcript_exon_variant	1/3	3
ALDH1A2	ENST00000558946.1	n.305A>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62478 AN: 151660 Hom.: 13128 Cov.: 29

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.365

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.400 AC: 12 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.409 AC XY: 9 AN XY: 22

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.409

GnomAD4 genome AF: 0.412 AC: 62533 AN: 151780 Hom.: 13142 Cov.: 29 AF XY: 0.407 AC XY: 30225 AN XY: 74176

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.403

Alfa AF: 0.405 Hom.: 6632

Bravo AF: 0.407

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	8.1
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1122208; hg19: chr15-58623525;