rs415799

Variant names:

• chr15-58398555-G-A
• rs415799
• ENST00000558239.5:c.-172+21416C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-58398555-G-A
• chr15-58398555-G-C
• chr15-58398555-G-T

Variant summary

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

The ENST00000558239.5(ALDH1A2):​c.-172+21416C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,100 control chromosomes in the GnomAD database, including 12,282 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 0.38 (12282 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 15 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.473 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+21416C>T		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+21416C>T		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57050 AN: 151982 Hom.: 12279 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.375 AC: 57079 AN: 152100 Hom.: 12282 Cov.: 32 AF XY: 0.373 AC XY: 27746 AN XY: 74346

African (AFR) AF: 0.175 AC: 7273 AN: 41480

American (AMR) AF: 0.480 AC: 7339 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1095 AN: 5164

South Asian (SAS) AF: 0.269 AC: 1298 AN: 4820

European-Finnish (FIN) AF: 0.443 AC: 4685 AN: 10566

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32457 AN: 68004

Other (OTH) AF: 0.394 AC: 833 AN: 2112

Alfa AF: 0.444 Hom.: 66895

Bravo AF: 0.374

Asia WGS AF: 0.240 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.72
PhyloP100		0.22

Splicing

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

Other links and lift over

dbSNP: rs415799; hg19: chr15-58690754;