rs16940213

Variant names:

• chr15-58403138-C-T
• rs16940213
• ENST00000558239.5:c.-172+16833G>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+16833G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,172 control chromosomes in the GnomAD database, including 2,098 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 0.16 (2098 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 8 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: Labcorp Genetics (formerly Invitae), G2P

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 (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558239.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A2	ENST00000558239.5	TSL:4	c.-172+16833G>A		intron	N/A	ENSP00000453292.1	Q9UED3
	ALDH1A2	ENST00000560863.5	TSL:4	n.415+16833G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23750 AN: 152054 Hom.: 2098 Cov.: 32

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.156 AC: 23759 AN: 152172 Hom.: 2098 Cov.: 32 AF XY: 0.158 AC XY: 11716 AN XY: 74380

African (AFR) AF: 0.0823 AC: 3421 AN: 41546

American (AMR) AF: 0.142 AC: 2165 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1495 AN: 5150

South Asian (SAS) AF: 0.190 AC: 917 AN: 4826

European-Finnish (FIN) AF: 0.185 AC: 1952 AN: 10574

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12532 AN: 68000

Other (OTH) AF: 0.162 AC: 341 AN: 2108

Alfa AF: 0.175 Hom.: 7846

Bravo AF: 0.150

Asia WGS AF: 0.241 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.31
DANN	Benign	0.73
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs16940213; hg19: chr15-58695337;