rs11855284

Variant names:

• chr15-58396988-T-C
• rs11855284
• ENST00000558239.5:c.-172+22983A>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+22983A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,180 control chromosomes in the GnomAD database, including 2,111 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 0.15 (2111 hom., cov: 33)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 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+22983A>G		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+22983A>G		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23444 AN: 152062 Hom.: 2112 Cov.: 33

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.154 AC: 23438 AN: 152180 Hom.: 2111 Cov.: 33 AF XY: 0.157 AC XY: 11686 AN XY: 74400

African (AFR) AF: 0.0560 AC: 2327 AN: 41572

American (AMR) AF: 0.210 AC: 3211 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3470

East Asian (EAS) AF: 0.120 AC: 621 AN: 5176

South Asian (SAS) AF: 0.216 AC: 1044 AN: 4830

European-Finnish (FIN) AF: 0.215 AC: 2266 AN: 10560

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12752 AN: 67968

Other (OTH) AF: 0.170 AC: 359 AN: 2114

Alfa AF: 0.178 Hom.: 3406

Bravo AF: 0.149

Asia WGS AF: 0.145 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.28
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs11855284; hg19: chr15-58689187;