Variant 15-57960864-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003888.4(ALDH1A2):c.1410-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,607,662 control chromosomes in the GnomAD database, including 151,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12645 hom., cov: 33)

Exomes 𝑓: 0.43 ( 139334 hom. )

Consequence

ALDH1A2
NM_003888.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.972

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:

ALDH1A2 (HGNC:):

ALDH1A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 15-57960864-C-T is Benign according to our data. Variant chr15-57960864-C-T is described in ClinVar as [Benign]. Clinvar id is 1276789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ALDH1A2	NM_003888.4 linkuse as main transcript	c.1410-20G>A	intron_variant	ENST00000249750.9	NP_003879.2	O94788-1
ALDH1A2	NM_001206897.2 linkuse as main transcript	c.1347-20G>A	intron_variant		NP_001193826.1	O94788-3
ALDH1A2	NM_170696.3 linkuse as main transcript	c.1296-20G>A	intron_variant		NP_733797.1	O94788-2
ALDH1A2	NM_170697.3 linkuse as main transcript	c.1122-20G>A	intron_variant		NP_733798.1	O94788-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9 linkuse as main transcript	c.1410-20G>A		intron_variant		1	NM_003888.4	ENSP00000249750.4		O94788-1

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60983

AN:

151922

Hom.:

12640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.462

Gnomad OTH

AF:

0.382

GnomAD3 exomes

AF:

0.369

AC:

92071

AN:

249460

Hom.:

18765

AF XY:

0.366

AC XY:

49356

AN XY:

134916

show subpopulations

Gnomad AFR exome

AF:

0.368

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.193

Gnomad SAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.466

Gnomad NFE exome

AF:

0.463

Gnomad OTH exome

AF:

0.393

GnomAD4 exome

AF:

0.429

AC:

624281

AN:

1455624

Hom.:

139334

Cov.:

AF XY:

0.422

AC XY:

305799

AN XY:

724544

show subpopulations

Gnomad4 AFR exome

AF:

0.366

Gnomad4 AMR exome

AF:

0.266

Gnomad4 ASJ exome

AF:

0.351

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.466

Gnomad4 NFE exome

AF:

0.466

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.401

AC:

61010

AN:

152038

Hom.:

12645

Cov.:

AF XY:

0.397

AC XY:

29477

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.367

Gnomad4 AMR

AF:

0.327

Gnomad4 ASJ

AF:

0.328

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.474

Gnomad4 NFE

AF:

0.462

Gnomad4 OTH

AF:

0.380

Alfa

AF:

0.433

Hom.:

20078

Bravo

AF:

0.392

Asia WGS

AF:

0.194

AC:

675

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.1

DANN

Benign

0.36

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over