15-58407738-C-T

Variant names:

• chr15-58407738-C-T
• rs13329672
• ENST00000558239.5:c.-172+12233G>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+12233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,116 control chromosomes in the GnomAD database, including 7,874 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 0.31 (7874 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 19 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 (AFR) allele frequency at 95% confidence interval = 0.438 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+12233G>A		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+12233G>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46841 AN: 151998 Hom.: 7857 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.308 AC: 46898 AN: 152116 Hom.: 7874 Cov.: 32 AF XY: 0.304 AC XY: 22626 AN XY: 74368

African (AFR) AF: 0.443 AC: 18372 AN: 41472

American (AMR) AF: 0.253 AC: 3865 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 987 AN: 3472

East Asian (EAS) AF: 0.167 AC: 866 AN: 5174

South Asian (SAS) AF: 0.303 AC: 1459 AN: 4816

European-Finnish (FIN) AF: 0.249 AC: 2640 AN: 10590

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17649 AN: 67994

Other (OTH) AF: 0.306 AC: 643 AN: 2104

Alfa AF: 0.266 Hom.: 9288

Bravo AF: 0.313

Asia WGS AF: 0.256 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.030
DANN	Benign	0.59
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs13329672; hg19: chr15-58699937;