15-57955365-C-G

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.1485-96G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,251,364 control chromosomes in the GnomAD database, including 112,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (11003 hom., cov: 32)
  • Exomes 𝑓: 0.42 (101203 hom.)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.66

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=-0.9).
• BP6: Variant 15-57955365-C-G is Benign according to our data. Variant chr15-57955365-C-G is described in ClinVar as [Benign]. Clinvar id is 1280142.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A2	NM_003888.4	c.1485-96G>C		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.1422-96G>C		intron_variant
ALDH1A2	NM_170696.3	c.1371-96G>C		intron_variant
ALDH1A2	NM_170697.3	c.1197-96G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.1485-96G>C		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55495 AN: 151938 Hom.: 11005 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.416 AC: 456777 AN: 1099308 Hom.: 101203 AF XY: 0.409 AC XY: 230201 AN XY: 563344

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.365 AC: 55501 AN: 152056 Hom.: 11003 Cov.: 32 AF XY: 0.361 AC XY: 26823 AN XY: 74288

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.350

Alfa AF: 0.316 Hom.: 1045

Bravo AF: 0.349

Asia WGS AF: 0.161 AC: 559 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	-0.90
Cadd	Benign	0.34
Dann	Benign	0.54

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: rs4646640; hg19: chr15-58247563; COSMIC: COSV51078169; COSMIC: COSV51078169;