rs16940027

Positions:

• chr15-58301531-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+118440A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 152,250 control chromosomes in the GnomAD database, including 655 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 0.070 (655 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 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+118440A>G		intron_variant		4
ALDH1A2	ENST00000558603.5	n.201+29648A>G		intron_variant, non_coding_transcript_variant		3
ALDH1A2	ENST00000558946.1	n.452+29648A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10628 AN: 152132 Hom.: 658 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.0756

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0709

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

GnomAD4 genome AF: 0.0698 AC: 10629 AN: 152250 Hom.: 655 Cov.: 32 AF XY: 0.0738 AC XY: 5493 AN XY: 74442

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.0859

Gnomad4 ASJ AF: 0.0756

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.0563

Gnomad4 NFE AF: 0.0533

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0653 Hom.: 537

Bravo AF: 0.0691

Asia WGS AF: 0.270 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16940027; hg19: chr15-58593730;