Genetic Variant ALDH1A2:c.*593C>G (chr15-57954604-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_003888.4(ALDH1A2):c.*593C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 166,114 control chromosomes in the GnomAD database, including 11,833 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 0.37 ( 11007 hom., cov: 33)

Exomes 𝑓: 0.32 ( 826 hom. )

Consequence

ALDH1A2
NM_003888.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.93

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A2	NM_003888.4 link	c.*593C>G	3_prime_UTR_variant	Exon 13 of 13	ENST00000249750.9	NP_003879.2	O94788-1
ALDH1A2	NM_001206897.2 link	c.*593C>G	3_prime_UTR_variant	Exon 14 of 14		NP_001193826.1	O94788-3
ALDH1A2	NM_170696.3 link	c.*593C>G	3_prime_UTR_variant	Exon 12 of 12		NP_733797.1	O94788-2
ALDH1A2	NM_170697.3 link	c.*593C>G	3_prime_UTR_variant	Exon 11 of 11		NP_733798.1	O94788-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750 link	c.*593C>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_003888.4	ENSP00000249750.4		O94788-1

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55559

AN:

151986

Hom.:

11009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.560

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.354

GnomAD4 exome

AF:

0.320

AC:

4480

AN:

14010

Hom.:

826

Cov.:

AF XY:

0.313

AC XY:

2316

AN XY:

7388

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.266

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.457

Gnomad4 NFE exome

AF:

0.420

Gnomad4 OTH exome

AF:

0.358

GnomAD4 genome

AF:

0.365

AC:

55565

AN:

152104

Hom.:

11007

Cov.:

AF XY:

0.361

AC XY:

26857

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.247

Gnomad4 AMR

AF:

0.302

Gnomad4 ASJ

AF:

0.326

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.475

Gnomad4 NFE

AF:

0.463

Gnomad4 OTH

AF:

0.351

Alfa

AF:

0.414

Hom.:

7520

Bravo

AF:

0.349

Asia WGS

AF:

0.163

AC:

567

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over