rs16940027

Variant names:

• chr15-58301531-T-C
• rs16940027
• ENST00000558239.5:c.-172+118440A>G

Variant summary

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

The ENST00000558239.5(ALDH1A2):​c.-172+118440A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 152,250 control chromosomes in the GnomAD database, including 655 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 0.070 (655 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 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+118440A>G		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000558603.5	n.201+29648A>G		intron_variant	Intron 1 of 2	3
ALDH1A2	ENST00000558946.1	n.452+29648A>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10628 AN: 152132 Hom.: 658 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.0756

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0709

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

GnomAD4 genome AF: 0.0698 AC: 10629 AN: 152250 Hom.: 655 Cov.: 32 AF XY: 0.0738 AC XY: 5493 AN XY: 74442

African (AFR) AF: 0.0465 AC: 1933 AN: 41560

American (AMR) AF: 0.0859 AC: 1314 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0756 AC: 262 AN: 3466

East Asian (EAS) AF: 0.332 AC: 1713 AN: 5166

South Asian (SAS) AF: 0.203 AC: 979 AN: 4820

European-Finnish (FIN) AF: 0.0563 AC: 598 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0533 AC: 3628 AN: 68016

Other (OTH) AF: 0.0716 AC: 151 AN: 2108

Alfa AF: 0.0630 Hom.: 575

Bravo AF: 0.0691

Asia WGS AF: 0.270 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.59
PhyloP100		0.33

Splicing

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

Other links and lift over

dbSNP: rs16940027; hg19: chr15-58593730;