15-58406811-C-T

Variant names:

• chr15-58406811-C-T
• rs11856159
• ENST00000558239.5:c.-172+13160G>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+13160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,136 control chromosomes in the GnomAD database, including 2,237 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 (2237 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 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+13160G>A		intron	N/A	ENSP00000453292.1	Q9UED3
	ALDH1A2	ENST00000560863.5	TSL:4	n.415+13160G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25179 AN: 152018 Hom.: 2236 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.166 AC: 25181 AN: 152136 Hom.: 2237 Cov.: 32 AF XY: 0.166 AC XY: 12367 AN XY: 74362

African (AFR) AF: 0.110 AC: 4552 AN: 41494

American (AMR) AF: 0.177 AC: 2709 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 625 AN: 3472

East Asian (EAS) AF: 0.132 AC: 684 AN: 5178

South Asian (SAS) AF: 0.217 AC: 1045 AN: 4818

European-Finnish (FIN) AF: 0.204 AC: 2162 AN: 10580

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12763 AN: 67996

Other (OTH) AF: 0.181 AC: 382 AN: 2108

Alfa AF: 0.162 Hom.: 1168

Bravo AF: 0.160

Asia WGS AF: 0.166 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.58
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs11856159; hg19: chr15-58699010;