rs16940213

chr15-58403138-C-T

Variant summary

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

The ENST00000558239.5(ALDH1A2):c.-172+16833G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,172 control chromosomes in the GnomAD database, including 2,098 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 0.16 (2098 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 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+16833G>A		intron_variant		4
ALDH1A2	ENST00000560863.5	n.415+16833G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23750 AN: 152054 Hom.: 2098 Cov.: 32

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.156 AC: 23759 AN: 152172 Hom.: 2098 Cov.: 32 AF XY: 0.158 AC XY: 11716 AN XY: 74380

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.162

Alfa AF: 0.181 Hom.: 5203

Bravo AF: 0.150

Asia WGS AF: 0.241 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.31
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16940213; hg19: chr15-58695337;