rs8041922

Positions:

• chr15-57983978-C-A
• chr15-57983978-C-G
• chr15-57983978-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000249750.9(ALDH1A2):​c.798+8727G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 152,270 control chromosomes in the GnomAD database, including 60,811 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 0.88 (60811 hom., cov: 33)
• Consequence: ALDH1A2 ENST00000249750.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A2	NM_003888.4	c.798+8727G>T		intron_variant		ENST00000249750.9	NP_003879.2
ALDH1A2	NM_001206897.2	c.735+8727G>T		intron_variant			NP_001193826.1
ALDH1A2	NM_170696.3	c.684+8967G>T		intron_variant			NP_733797.1
ALDH1A2	NM_170697.3	c.510+8727G>T		intron_variant			NP_733798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.798+8727G>T		intron_variant		1	NM_003888.4	ENSP00000249750	P1

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134469 AN: 152152 Hom.: 60789 Cov.: 33

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.884 AC: 134543 AN: 152270 Hom.: 60811 Cov.: 33 AF XY: 0.888 AC XY: 66079 AN XY: 74454

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.949

Gnomad4 ASJ AF: 0.948

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.984

Gnomad4 FIN AF: 0.969

Gnomad4 NFE AF: 0.966

Gnomad4 OTH AF: 0.916

Alfa AF: 0.919 Hom.: 8432

Bravo AF: 0.872

Asia WGS AF: 0.978 AC: 3403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0040
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs8041922; hg19: chr15-58276176;