chr15-58137065-G-A

Position:

• chr15-58137065-G-A

Variant summary

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

The ENST00000558231.5(ALDH1A2):​c.31-122784C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,128 control chromosomes in the GnomAD database, including 23,798 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 0.56 (23798 hom., cov: 33)
• Consequence: ALDH1A2 ENST00000558231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000557967.5	c.-172+1382C>T		intron_variant		4		ENSP00000454028
ALDH1A2	ENST00000558231.5	c.31-122784C>T		intron_variant		2		ENSP00000453600
ALDH1A2	ENST00000558239.5	c.-171-122784C>T		intron_variant		4		ENSP00000453292

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84380 AN: 152010 Hom.: 23775 Cov.: 33

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.555 AC: 84452 AN: 152128 Hom.: 23798 Cov.: 33 AF XY: 0.551 AC XY: 40996 AN XY: 74358

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.541

Alfa AF: 0.524 Hom.: 41276

Bravo AF: 0.566

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1516400; hg19: chr15-58429264;