15-57960908-T-C

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.1410-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,463,828 control chromosomes in the GnomAD database, including 133,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (11132 hom., cov: 33)
  • Exomes 𝑓: 0.42 (122302 hom.)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0730

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=-0.84).
• BP6: Variant 15-57960908-T-C is Benign according to our data. Variant chr15-57960908-T-C is described in ClinVar as [Benign]. Clinvar id is 1239011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A2	NM_003888.4	c.1410-64A>G		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.1347-64A>G		intron_variant
ALDH1A2	NM_170696.3	c.1296-64A>G		intron_variant
ALDH1A2	NM_170697.3	c.1122-64A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.1410-64A>G		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56231 AN: 152006 Hom.: 11131 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.422 AC: 553104 AN: 1311704 Hom.: 122302 Cov.: 19 AF XY: 0.415 AC XY: 273269 AN XY: 658638

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.370 AC: 56246 AN: 152124 Hom.: 11132 Cov.: 33 AF XY: 0.365 AC XY: 27172 AN XY: 74350

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.356

Alfa AF: 0.426 Hom.: 18649

Bravo AF: 0.355

Asia WGS AF: 0.173 AC: 603 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.47
Dann	Benign	0.47

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: rs3784262; hg19: chr15-58253106;