15-57961980-T-A

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.1251+32A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,613,580 control chromosomes in the GnomAD database, including 457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (208 hom., cov: 32)
  • Exomes 𝑓: 0.011 (249 hom.)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72

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=-0.77).
• BP6: Variant 15-57961980-T-A is Benign according to our data. Variant chr15-57961980-T-A is described in ClinVar as [Benign]. Clinvar id is 1257533.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A2	NM_003888.4	c.1251+32A>T		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.1188+32A>T		intron_variant
ALDH1A2	NM_170696.3	c.1137+32A>T		intron_variant
ALDH1A2	NM_170697.3	c.963+32A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.1251+32A>T		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5026 AN: 152158 Hom.: 205 Cov.: 32

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00823

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.0179 AC: 4487 AN: 251370 Hom.: 113 AF XY: 0.0158 AC XY: 2148 AN XY: 135850

Gnomad AFR exome AF: 0.0938

Gnomad AMR exome AF: 0.0381

Gnomad ASJ exome AF: 0.00755

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0112

Gnomad FIN exome AF: 0.00208

Gnomad NFE exome AF: 0.00950

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0111 AC: 16199 AN: 1461304 Hom.: 249 Cov.: 31 AF XY: 0.0108 AC XY: 7845 AN XY: 727022

Gnomad4 AFR exome AF: 0.0918

Gnomad4 AMR exome AF: 0.0373

Gnomad4 ASJ exome AF: 0.00784

Gnomad4 EAS exome AF: 0.000554

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.00264

Gnomad4 NFE exome AF: 0.00827

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome AF: 0.0331 AC: 5042 AN: 152276 Hom.: 208 Cov.: 32 AF XY: 0.0327 AC XY: 2436 AN XY: 74464

Gnomad4 AFR AF: 0.0927

Gnomad4 AMR AF: 0.0311

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.00822

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00914 Hom.: 7

Bravo AF: 0.0385

Asia WGS AF: 0.0150 AC: 53 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

Jun 18, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.056
Dann	Benign	0.78

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: rs35153668; hg19: chr15-58254178;