15-58341448-A-G

Variant names:

• chr15-58341448-A-G
• rs382086
• ENST00000558239.5:c.-172+78523T>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+78523T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,974 control chromosomes in the GnomAD database, including 32,201 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 0.65 (32201 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 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+78523T>C		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+78523T>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98353 AN: 151856 Hom.: 32181 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.648 AC: 98424 AN: 151974 Hom.: 32201 Cov.: 32 AF XY: 0.643 AC XY: 47746 AN XY: 74304

African (AFR) AF: 0.636 AC: 26345 AN: 41450

American (AMR) AF: 0.619 AC: 9457 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2706 AN: 3472

East Asian (EAS) AF: 0.438 AC: 2260 AN: 5164

South Asian (SAS) AF: 0.577 AC: 2777 AN: 4812

European-Finnish (FIN) AF: 0.680 AC: 7162 AN: 10538

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45591 AN: 67956

Other (OTH) AF: 0.655 AC: 1379 AN: 2106

Alfa AF: 0.665 Hom.: 128797

Bravo AF: 0.645

Asia WGS AF: 0.577 AC: 1997 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.85
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs382086; hg19: chr15-58633647;