rs183786

Variant names:

• chr15-58375911-C-T
• rs183786
• ENST00000558239.5:c.-172+44060G>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+44060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,088 control chromosomes in the GnomAD database, including 3,842 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 0.17 (3842 hom., cov: 33)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 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+44060G>A		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+44060G>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25923 AN: 151970 Hom.: 3816 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.171 AC: 26001 AN: 152088 Hom.: 3842 Cov.: 33 AF XY: 0.172 AC XY: 12773 AN XY: 74352

African (AFR) AF: 0.388 AC: 16079 AN: 41426

American (AMR) AF: 0.0805 AC: 1230 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3466

East Asian (EAS) AF: 0.326 AC: 1686 AN: 5172

South Asian (SAS) AF: 0.158 AC: 764 AN: 4824

European-Finnish (FIN) AF: 0.113 AC: 1191 AN: 10584

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0668 AC: 4544 AN: 68018

Other (OTH) AF: 0.131 AC: 276 AN: 2112

Alfa AF: 0.0935 Hom.: 2255

Bravo AF: 0.177

Asia WGS AF: 0.210 AC: 733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.50
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs183786; hg19: chr15-58668110;