rs6493978

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003888.4(ALDH1A2):​c.118-19515G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 148,950 control chromosomes in the GnomAD database, including 16,246 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 0.46 ( 16246 hom., cov: 26)

Consequence

ALDH1A2
NM_003888.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.76
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.03).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ALDH1A2NM_003888.4 linkuse as main transcriptc.118-19515G>A intron_variant ENST00000249750.9
ALDH1A2NM_001206897.2 linkuse as main transcriptc.55-19515G>A intron_variant
ALDH1A2NM_170696.3 linkuse as main transcriptc.118-19515G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ALDH1A2ENST00000249750.9 linkuse as main transcriptc.118-19515G>A intron_variant 1 NM_003888.4 P1O94788-1

Frequencies

GnomAD3 genomes
AF:
0.461
AC:
68689
AN:
148842
Hom.:
16238
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.392
Gnomad AMI
AF:
0.567
Gnomad AMR
AF:
0.416
Gnomad ASJ
AF:
0.434
Gnomad EAS
AF:
0.307
Gnomad SAS
AF:
0.261
Gnomad FIN
AF:
0.550
Gnomad MID
AF:
0.468
Gnomad NFE
AF:
0.527
Gnomad OTH
AF:
0.453
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.461
AC:
68718
AN:
148950
Hom.:
16246
Cov.:
26
AF XY:
0.458
AC XY:
33224
AN XY:
72468
show subpopulations
Gnomad4 AFR
AF:
0.392
Gnomad4 AMR
AF:
0.416
Gnomad4 ASJ
AF:
0.434
Gnomad4 EAS
AF:
0.307
Gnomad4 SAS
AF:
0.261
Gnomad4 FIN
AF:
0.550
Gnomad4 NFE
AF:
0.527
Gnomad4 OTH
AF:
0.451
Alfa
AF:
0.492
Hom.:
2321
Bravo
AF:
0.452
Asia WGS
AF:
0.286
AC:
989
AN:
3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.13
DANN
Benign
0.099

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.

Other links and lift over

dbSNP: rs6493978; hg19: chr15-58325994; API