15-57960864-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.972

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A2	NM_003888.4	c.1410-20G>A		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.1347-20G>A		intron_variant
ALDH1A2	NM_170696.3	c.1296-20G>A		intron_variant
ALDH1A2	NM_170697.3	c.1122-20G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.1410-20G>A		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60983 AN: 151922 Hom.: 12640 Cov.: 33

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

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.: 30 AF XY: 0.422 AC XY: 305799 AN XY: 724544

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.: 33 AF XY: 0.397 AC XY: 29477 AN XY: 74318

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

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

Other links and lift over

dbSNP: rs3784263; hg19: chr15-58253062; COSMIC: COSV51078173;