rs920915

Variant names:

• chr15-58396268-C-G
• rs920915
• ENST00000558239.5:c.-172+23703G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000558239.5(ALDH1A2):​c.-172+23703G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,614 control chromosomes in the GnomAD database, including 23,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.55 (23865 hom., cov: 34)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.216
• Publications: 34 publications found

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]

ALDH1A2 Gene-Disease associations (from GenCC):

• diaphragmatic hernia 4, with cardiovascular defects

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000558239.5	c.-172+23703G>C		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+23703G>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83782 AN: 151494 Hom.: 23836 Cov.: 34

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.553 AC: 83862 AN: 151614 Hom.: 23865 Cov.: 34 AF XY: 0.557 AC XY: 41224 AN XY: 74064

African (AFR) AF: 0.643 AC: 26603 AN: 41352

American (AMR) AF: 0.488 AC: 7443 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3466

East Asian (EAS) AF: 0.782 AC: 4008 AN: 5128

South Asian (SAS) AF: 0.699 AC: 3372 AN: 4822

European-Finnish (FIN) AF: 0.531 AC: 5557 AN: 10464

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33520 AN: 67838

Other (OTH) AF: 0.536 AC: 1129 AN: 2106

Alfa AF: 0.508 Hom.: 11024

Bravo AF: 0.552

Asia WGS AF: 0.737 AC: 2563 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

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Department of Ophthalmology and Visual Sciences Kyoto University

Significance: not provided

Review Status: no classification provided

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs920915; hg19: chr15-58688467;