15-57961071-T-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.1409+66A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,589,194 control chromosomes in the GnomAD database, including 148,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12233 hom., cov: 32)
  • Exomes 𝑓: 0.43 (136262 hom.)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.08

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=-0.85).
• BP6: Variant 15-57961071-T-G is Benign according to our data. Variant chr15-57961071-T-G is described in ClinVar as [Benign]. Clinvar id is 1226239.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.1409+66A>C		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.1346+66A>C		intron_variant
ALDH1A2	NM_170696.3	c.1295+66A>C		intron_variant
ALDH1A2	NM_170697.3	c.1121+66A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.1409+66A>C		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59808 AN: 151876 Hom.: 12229 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.426 AC: 612344 AN: 1437200 Hom.: 136262 Cov.: 29 AF XY: 0.419 AC XY: 300441 AN XY: 716276

Gnomad4 AFR exome AF: 0.337

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.349

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.398

GnomAD4 genome AF: 0.394 AC: 59834 AN: 151994 Hom.: 12233 Cov.: 32 AF XY: 0.390 AC XY: 28941 AN XY: 74292

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.369

Alfa AF: 0.429 Hom.: 18089

Bravo AF: 0.384

Asia WGS AF: 0.186 AC: 645 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	-0.85
Cadd	Benign	0.14
Dann	Benign	0.66

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: rs3784260; hg19: chr15-58253269; COSMIC: COSV51081998;