rs10468017

Variant names:

• chr15-58386313-C-T
• rs10468017
• ENST00000558239.5:c.-172+33658G>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+33658G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,102 control chromosomes in the GnomAD database, including 4,850 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 0.24 (4850 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 185 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558239.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A2	ENST00000558239.5	TSL:4	c.-172+33658G>A		intron	N/A	ENSP00000453292.1
	ALDH1A2	ENST00000560863.5	TSL:4	n.415+33658G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36702 AN: 151984 Hom.: 4847 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.241 AC: 36717 AN: 152102 Hom.: 4850 Cov.: 32 AF XY: 0.241 AC XY: 17950 AN XY: 74342

African (AFR) AF: 0.161 AC: 6690 AN: 41504

American (AMR) AF: 0.221 AC: 3386 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 883 AN: 3472

East Asian (EAS) AF: 0.189 AC: 976 AN: 5170

South Asian (SAS) AF: 0.192 AC: 925 AN: 4816

European-Finnish (FIN) AF: 0.341 AC: 3598 AN: 10556

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19423 AN: 67976

Other (OTH) AF: 0.249 AC: 526 AN: 2114

Alfa AF: 0.267 Hom.: 20832

Bravo AF: 0.228

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.84
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs10468017; hg19: chr15-58678512;