rs12591551

Variant names:

• chr15-57989605-C-A
• rs12591551
• NM_003888.4:c.798+3100G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-57989605-C-A
• chr15-57989605-C-T

Variant summary

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

The NM_003888.4(ALDH1A2):​c.798+3100G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 151,974 control chromosomes in the GnomAD database, including 587 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 0.087 (587 hom., cov: 32)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A2	NM_003888.4	c.798+3100G>T		intron_variant	Intron 7 of 12	ENST00000249750.9	NP_003879.2
ALDH1A2	NM_001206897.2	c.735+3100G>T		intron_variant	Intron 8 of 13		NP_001193826.1
ALDH1A2	NM_170696.3	c.684+3340G>T		intron_variant	Intron 6 of 11		NP_733797.1
ALDH1A2	NM_170697.3	c.510+3100G>T		intron_variant	Intron 5 of 10		NP_733798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.798+3100G>T		intron_variant	Intron 7 of 12	1	NM_003888.4	ENSP00000249750.4

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13231 AN: 151856 Hom.: 584 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0871 AC: 13243 AN: 151974 Hom.: 587 Cov.: 32 AF XY: 0.0891 AC XY: 6619 AN XY: 74290

African (AFR) AF: 0.105 AC: 4369 AN: 41438

American (AMR) AF: 0.0912 AC: 1393 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 240 AN: 3470

East Asian (EAS) AF: 0.124 AC: 642 AN: 5172

South Asian (SAS) AF: 0.0905 AC: 436 AN: 4820

European-Finnish (FIN) AF: 0.0762 AC: 803 AN: 10532

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0751 AC: 5104 AN: 67952

Other (OTH) AF: 0.0833 AC: 176 AN: 2112

Alfa AF: 0.0237 Hom.: 14

Bravo AF: 0.0898

Asia WGS AF: 0.100 AC: 346 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	1.9
DANN	Benign	0.72
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12591551; hg19: chr15-58281803;