rs1816879

Variant names:

• chr15-58318356-G-A
• rs1816879
• ENST00000558239.5:c.-172+101615C>T

Variant summary

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

The ENST00000558239.5(ALDH1A2):​c.-172+101615C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,998 control chromosomes in the GnomAD database, including 4,187 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 0.22 (4187 hom., cov: 31)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 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+101615C>T		intron	N/A	ENSP00000453292.1	Q9UED3
	ALDH1A2	ENST00000558603.5	TSL:3	n.201+12823C>T		intron	N/A
	ALDH1A2	ENST00000558946.1	TSL:4	n.452+12823C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33109 AN: 151878 Hom.: 4188 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.218 AC: 33114 AN: 151998 Hom.: 4187 Cov.: 31 AF XY: 0.212 AC XY: 15743 AN XY: 74286

African (AFR) AF: 0.104 AC: 4305 AN: 41492

American (AMR) AF: 0.206 AC: 3145 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 795 AN: 3468

East Asian (EAS) AF: 0.135 AC: 695 AN: 5164

South Asian (SAS) AF: 0.209 AC: 1004 AN: 4814

European-Finnish (FIN) AF: 0.189 AC: 1993 AN: 10548

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20254 AN: 67928

Other (OTH) AF: 0.241 AC: 509 AN: 2110

Alfa AF: 0.273 Hom.: 10182

Bravo AF: 0.215

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.4
DANN	Benign	0.77
PhyloP100		0.057

Splicing

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

Other links and lift over

dbSNP: rs1816879; hg19: chr15-58610555;