15-57965649-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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0410

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 15-57965649-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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A2	NM_003888.4	c.901+76G>A		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.838+76G>A		intron_variant
ALDH1A2	NM_170696.3	c.787+76G>A		intron_variant
ALDH1A2	NM_170697.3	c.613+76G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.901+76G>A		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69213 AN: 151938 Hom.: 16300 Cov.: 33

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

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.: 33 AF XY: 0.453 AC XY: 33687 AN XY: 74344

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: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	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

Other links and lift over

dbSNP: rs3784259; hg19: chr15-58257847; COSMIC: COSV51082695; COSMIC: COSV51082695;