ENST00000558239.5:c.-172+82151C>A

Variant names:

• chr15-58337820-G-T
• rs12910827
• ENST00000558239.5:c.-172+82151C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000558239.5(ALDH1A2):​c.-172+82151C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 152,226 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.036 (103 hom., cov: 33)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 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+82151C>A		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+82151C>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5406 AN: 152108 Hom.: 103 Cov.: 33

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0154

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0335

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

GnomAD4 genome AF: 0.0355 AC: 5405 AN: 152226 Hom.: 103 Cov.: 33 AF XY: 0.0348 AC XY: 2593 AN XY: 74412

African (AFR) AF: 0.0589 AC: 2444 AN: 41528

American (AMR) AF: 0.0281 AC: 430 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3468

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5192

South Asian (SAS) AF: 0.0154 AC: 74 AN: 4814

European-Finnish (FIN) AF: 0.0313 AC: 332 AN: 10606

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0295 AC: 2009 AN: 68016

Other (OTH) AF: 0.0331 AC: 70 AN: 2112

Alfa AF: 0.0283 Hom.: 75

Bravo AF: 0.0359

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs12910827; hg19: chr15-58630019;