ENST00000558231.5:c.31-122784C>T

Variant names:

• chr15-58137065-G-A
• rs1516400
• ENST00000558231.5:c.31-122784C>T

Variant summary

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

The ENST00000558231.5(ALDH1A2):​c.31-122784C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,128 control chromosomes in the GnomAD database, including 23,798 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 0.56 (23798 hom., cov: 33)
• Consequence: ALDH1A2 ENST00000558231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 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	ENST00000558231.5	c.31-122784C>T		intron_variant	Intron 1 of 12	2		ENSP00000453600.1
ALDH1A2	ENST00000558239.5	c.-171-122784C>T		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000557967.5	c.-172+1382C>T		intron_variant	Intron 1 of 2	4		ENSP00000454028.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84380 AN: 152010 Hom.: 23775 Cov.: 33

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.555 AC: 84452 AN: 152128 Hom.: 23798 Cov.: 33 AF XY: 0.551 AC XY: 40996 AN XY: 74358

African (AFR) AF: 0.644 AC: 26730 AN: 41490

American (AMR) AF: 0.545 AC: 8328 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1846 AN: 3470

East Asian (EAS) AF: 0.495 AC: 2556 AN: 5166

South Asian (SAS) AF: 0.396 AC: 1911 AN: 4822

European-Finnish (FIN) AF: 0.500 AC: 5295 AN: 10582

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35920 AN: 67986

Other (OTH) AF: 0.541 AC: 1145 AN: 2116

Alfa AF: 0.533 Hom.: 91064

Bravo AF: 0.566

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.49
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1516400; hg19: chr15-58429264;