rs8036597

Variant names:

• chr15-58357469-C-G
• rs8036597
• ENST00000558239.5:c.-172+62502G>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+62502G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,928 control chromosomes in the GnomAD database, including 10,404 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 0.36 (10404 hom., cov: 31)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 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+62502G>C		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+62502G>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54984 AN: 151810 Hom.: 10391 Cov.: 31

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.362 AC: 55017 AN: 151928 Hom.: 10404 Cov.: 31 AF XY: 0.364 AC XY: 27028 AN XY: 74220

African (AFR) AF: 0.309 AC: 12798 AN: 41430

American (AMR) AF: 0.252 AC: 3854 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1244 AN: 3470

East Asian (EAS) AF: 0.192 AC: 989 AN: 5158

South Asian (SAS) AF: 0.432 AC: 2078 AN: 4812

European-Finnish (FIN) AF: 0.513 AC: 5406 AN: 10532

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27393 AN: 67944

Other (OTH) AF: 0.337 AC: 708 AN: 2100

Alfa AF: 0.392 Hom.: 1482

Bravo AF: 0.338

Asia WGS AF: 0.340 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.19
DANN	Benign	0.41
PhyloP100		-0.96

Splicing

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

Other links and lift over

dbSNP: rs8036597; hg19: chr15-58649668;