rs4646642

Positions:

• chr15-57954718-A-G

Variant summary

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

The NM_003888.4(ALDH1A2):​c.*479T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 188,732 control chromosomes in the GnomAD database, including 21,345 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 0.47 (17390 hom., cov: 32)
  • Exomes 𝑓: 0.44 (3955 hom.)
• Consequence: ALDH1A2 NM_003888.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

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=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A2	NM_003888.4	c.*479T>C		3_prime_UTR_variant	13/13	ENST00000249750.9	NP_003879.2
ALDH1A2	NM_001206897.2	c.*479T>C		3_prime_UTR_variant	14/14		NP_001193826.1
ALDH1A2	NM_170696.3	c.*479T>C		3_prime_UTR_variant	12/12		NP_733797.1
ALDH1A2	NM_170697.3	c.*479T>C		3_prime_UTR_variant	11/11		NP_733798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.*479T>C		3_prime_UTR_variant	13/13	1	NM_003888.4	ENSP00000249750	P1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71519 AN: 151800 Hom.: 17384 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.442 AC: 16282 AN: 36814 Hom.: 3955 Cov.: 0 AF XY: 0.433 AC XY: 8181 AN XY: 18886

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.514

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.456

GnomAD4 genome AF: 0.471 AC: 71547 AN: 151918 Hom.: 17390 Cov.: 32 AF XY: 0.468 AC XY: 34729 AN XY: 74232

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.453

Alfa AF: 0.523 Hom.: 30842

Bravo AF: 0.459

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4646642; hg19: chr15-58246916; COSMIC: COSV51082898; COSMIC: COSV51082898;