Variant 15-57965649-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.901+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,047,776 control chromosomes in the GnomAD database, including 125,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16307 hom., cov: 33)

Exomes 𝑓: 0.48 ( 108802 hom. )

Consequence

ALDH1A2
NM_003888.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0410

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 -20 ACMG points.

BP4

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

BP6

Variant 15-57965649-C-T is Benign according to our data. Variant chr15-57965649-C-T is described in ClinVar as [Benign]. Clinvar id is 1241238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ALDH1A2	NM_003888.4 link	c.901+76G>A	intron_variant	ENST00000249750.9	NP_003879.2	O94788-1
ALDH1A2	NM_001206897.2 link	c.838+76G>A	intron_variant		NP_001193826.1	O94788-3
ALDH1A2	NM_170696.3 link	c.787+76G>A	intron_variant		NP_733797.1	O94788-2
ALDH1A2	NM_170697.3 link	c.613+76G>A	intron_variant		NP_733798.1	O94788-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9 link	c.901+76G>A		intron_variant		1	NM_003888.4	ENSP00000249750.4		O94788-1

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69213

AN:

151938

Hom.:

16300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.603

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.546

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.528

Gnomad OTH

AF:

0.443

GnomAD4 exome

AF:

0.483

AC:

432959

AN:

895720

Hom.:

108802

AF XY:

0.476

AC XY:

223397

AN XY:

468918

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.336

Gnomad4 ASJ exome

AF:

0.405

Gnomad4 EAS exome

AF:

0.290

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.537

Gnomad4 NFE exome

AF:

0.535

Gnomad4 OTH exome

AF:

0.464

GnomAD4 genome

AF:

0.455

AC:

69241

AN:

152056

Hom.:

16307

Cov.:

AF XY:

0.453

AC XY:

33687

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.399

Gnomad4 ASJ

AF:

0.390

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.546

Gnomad4 NFE

AF:

0.528

Gnomad4 OTH

AF:

0.440

Alfa

AF:

0.492

Hom.:

8349

Bravo

AF:

0.444

Asia WGS

AF:

0.283

AC:

983

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

1.6

DANN

Benign

0.26

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