ENST00000558239.5:c.-172+18150C>A

Variant names:

• chr15-58401821-G-T
• rs16940212
• ENST00000558239.5:c.-172+18150C>A

Variant summary

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

The ENST00000558239.5(ALDH1A2):​c.-172+18150C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,164 control chromosomes in the GnomAD database, including 2,142 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 0.16 (2142 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 27 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 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+18150C>A		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+18150C>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24188 AN: 152046 Hom.: 2144 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.159 AC: 24193 AN: 152164 Hom.: 2142 Cov.: 32 AF XY: 0.160 AC XY: 11934 AN XY: 74384

African (AFR) AF: 0.0846 AC: 3515 AN: 41532

American (AMR) AF: 0.139 AC: 2134 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1477 AN: 5156

South Asian (SAS) AF: 0.184 AC: 888 AN: 4824

European-Finnish (FIN) AF: 0.210 AC: 2224 AN: 10574

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12786 AN: 67988

Other (OTH) AF: 0.159 AC: 337 AN: 2114

Alfa AF: 0.177 Hom.: 7735

Bravo AF: 0.151

Asia WGS AF: 0.238 AC: 826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.97
DANN	Benign	0.44
PhyloP100		0.067

Splicing

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

Other links and lift over

dbSNP: rs16940212; hg19: chr15-58694020;