15-58244196-C-G

Position:

• chr15-58244196-C-G

Variant summary

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

The ENST00000558231.5(ALDH1A2):​c.30+34978G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,104 control chromosomes in the GnomAD database, including 21,066 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 0.52 (21066 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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]

ALDH1A2 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124903499	XR_007064653.1	n.177-57C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000558231.5	c.30+34978G>C		intron_variant		2		ENSP00000453600.1
ALDH1A2	ENST00000558239.5	c.-172+175775G>C		intron_variant		4		ENSP00000453292.1
ALDH1A2	ENST00000558073.5	n.265+1939G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78653 AN: 151988 Hom.: 21067 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.517 AC: 78685 AN: 152104 Hom.: 21066 Cov.: 32 AF XY: 0.513 AC XY: 38179 AN XY: 74368

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.506

Alfa AF: 0.435 Hom.: 1258

Bravo AF: 0.504

Asia WGS AF: 0.389 AC: 1354 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	1.8
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8034444; hg19: chr15-58536395;