chr15-58391167-A-G

Variant names:

• chr15-58391167-A-G
• rs1532085
• ENST00000558239.5:c.-172+28804T>C

Variant summary

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

The ENST00000558239.5(ALDH1A2):​c.-172+28804T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,070 control chromosomes in the GnomAD database, including 25,193 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 0.57 (25193 hom., cov: 33)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914
• Publications: 197 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.62 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+28804T>C		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+28804T>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86685 AN: 151952 Hom.: 25183 Cov.: 33

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.570 AC: 86740 AN: 152070 Hom.: 25193 Cov.: 33 AF XY: 0.566 AC XY: 42037 AN XY: 74334

African (AFR) AF: 0.480 AC: 19920 AN: 41482

American (AMR) AF: 0.610 AC: 9312 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2201 AN: 3468

East Asian (EAS) AF: 0.515 AC: 2660 AN: 5164

South Asian (SAS) AF: 0.467 AC: 2252 AN: 4824

European-Finnish (FIN) AF: 0.561 AC: 5929 AN: 10564

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42499 AN: 67986

Other (OTH) AF: 0.587 AC: 1241 AN: 2114

Alfa AF: 0.609 Hom.: 136161

Bravo AF: 0.574

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.22
PhyloP100		-0.91

Splicing

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

Other links and lift over

dbSNP: rs1532085; hg19: chr15-58683366;