rs10518973

Variant names:

• chr15-58359381-A-C
• rs10518973
• ENST00000558239.5:c.-172+60590T>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+60590T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,114 control chromosomes in the GnomAD database, including 4,998 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 0.24 (4998 hom., cov: 31)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.965
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 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+60590T>G		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+60590T>G		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35908 AN: 151996 Hom.: 4999 Cov.: 31

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.236 AC: 35906 AN: 152114 Hom.: 4998 Cov.: 31 AF XY: 0.237 AC XY: 17592 AN XY: 74342

African (AFR) AF: 0.0875 AC: 3635 AN: 41546

American (AMR) AF: 0.236 AC: 3612 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1569 AN: 5152

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4820

European-Finnish (FIN) AF: 0.285 AC: 3013 AN: 10556

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21276 AN: 67966

Other (OTH) AF: 0.255 AC: 538 AN: 2112

Alfa AF: 0.284 Hom.: 20865

Bravo AF: 0.224

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.80
PhyloP100		0.96

Splicing

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

Other links and lift over

dbSNP: rs10518973; hg19: chr15-58651580;