15-57955467-AAAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003888.4(ALDH1A2):c.1485-201_1485-199del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 152,190 control chromosomes in the GnomAD database, including 759 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.097 (759 hom., cov: 31)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.25

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 -10 ACMG points.

• BP6: Variant 15-57955467-AAAG-A is Benign according to our data. Variant chr15-57955467-AAAG-A is described in ClinVar as [Benign]. Clinvar id is 1232066.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A2	NM_003888.4	c.1485-201_1485-199del		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.1422-201_1422-199del		intron_variant
ALDH1A2	NM_170696.3	c.1371-201_1371-199del		intron_variant
ALDH1A2	NM_170697.3	c.1197-201_1197-199del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.1485-201_1485-199del		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14719 AN: 152074 Hom.: 757 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0989

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.0908

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0968 AC: 14733 AN: 152190 Hom.: 759 Cov.: 31 AF XY: 0.0983 AC XY: 7311 AN XY: 74402

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0704

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0990

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.0759

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0299 Hom.: 21

Bravo AF: 0.101

Asia WGS AF: 0.117 AC: 406 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

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: rs3051364; hg19: chr15-58247665;