rs1816879

chr15-58318356-G-A

Variant summary

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

The ENST00000558239.5(ALDH1A2):c.-172+101615C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,998 control chromosomes in the GnomAD database, including 4,187 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 0.22 (4187 hom., cov: 31)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 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+101615C>T		intron_variant		4
ALDH1A2	ENST00000558603.5	n.201+12823C>T		intron_variant, non_coding_transcript_variant		3
ALDH1A2	ENST00000558946.1	n.452+12823C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33109 AN: 151878 Hom.: 4188 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.218 AC: 33114 AN: 151998 Hom.: 4187 Cov.: 31 AF XY: 0.212 AC XY: 15743 AN XY: 74286

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.241

Alfa AF: 0.280 Hom.: 8379

Bravo AF: 0.215

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.4
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1816879; hg19: chr15-58610555;