Genetic Variant ALDH1A2:n.54A>G (chr15-58331326-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000558603.5(ALDH1A2):n.54A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,810 control chromosomes in the GnomAD database, including 13,143 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 0.41 ( 13142 hom., cov: 29)

Exomes 𝑓: 0.40 ( 1 hom. )

Consequence

ALDH1A2
ENST00000558603.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.368

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

diaphragmatic hernia 4, with cardiovascular defects
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ALDH1A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ALDH1A2	ENST00000558603.5 link	n.54A>G	non_coding_transcript_exon_variant	Exon 1 of 3	3
ALDH1A2	ENST00000558946.1 link	n.305A>G	non_coding_transcript_exon_variant	Exon 1 of 2	4
ALDH1A2	ENST00000561098.1 link	n.139A>G	non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62478

AN:

151660

Hom.:

13128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.570

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.345

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.365

Gnomad NFE

AF:

0.410

Gnomad OTH

AF:

0.407

GnomAD4 exome

AF:

0.400

AC:

AN:

Hom.:

Cov.:

AF XY:

0.409

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.409

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.412

AC:

62533

AN:

151780

Hom.:

13142

Cov.:

AF XY:

0.407

AC XY:

30225

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.479

AC:

19796

AN:

41362

American (AMR)

AF:

0.297

AC:

4527

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

1098

AN:

3468

East Asian (EAS)

AF:

0.345

AC:

1780

AN:

5154

South Asian (SAS)

AF:

0.355

AC:

1699

AN:

4784

European-Finnish (FIN)

AF:

0.411

AC:

4337

AN:

10544

Middle Eastern (MID)

AF:

0.369

AC:

107

AN:

290

European-Non Finnish (NFE)

AF:

0.410

AC:

27822

AN:

67908

Other (OTH)

AF:

0.403

AC:

849

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1771

3542

5312

7083

8854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.403

Hom.:

9377

Bravo

AF:

0.407

Asia WGS

AF:

0.303

AC:

1055

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.1

(source)

DANN

Benign

0.85

PhyloP100

-0.37

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over