chr15-58014104-G-A

Position:

• chr15-58014104-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003888.4(ALDH1A2):​c.222+73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 1,613,864 control chromosomes in the GnomAD database, including 383 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 0.014 (22 hom., cov: 32)
  • Exomes 𝑓: 0.020 (361 hom.)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0144 (2192/152334) while in subpopulation NFE AF= 0.0209 (1423/68032). AF 95% confidence interval is 0.02. There are 22 homozygotes in gnomad4. There are 1041 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A2	NM_003888.4	c.222+73C>T		intron_variant		ENST00000249750.9	NP_003879.2
ALDH1A2	NM_001206897.2	c.159+73C>T		intron_variant			NP_001193826.1
ALDH1A2	NM_170696.3	c.222+73C>T		intron_variant			NP_733797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.222+73C>T		intron_variant		1	NM_003888.4	ENSP00000249750.4

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2192 AN: 152216 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00393

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0255

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.0196 AC: 28589 AN: 1461530 Hom.: 361 Cov.: 31 AF XY: 0.0192 AC XY: 13961 AN XY: 727076

Gnomad4 AFR exome AF: 0.00299

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.0228

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00444

Gnomad4 FIN exome AF: 0.0229

Gnomad4 NFE exome AF: 0.0222

Gnomad4 OTH exome AF: 0.0170

GnomAD4 genome AF: 0.0144 AC: 2192 AN: 152334 Hom.: 22 Cov.: 32 AF XY: 0.0140 AC XY: 1041 AN XY: 74492

Gnomad4 AFR AF: 0.00392

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0255

Gnomad4 NFE AF: 0.0209

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00815 Hom.: 4

Bravo AF: 0.0133

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.8
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35667670; hg19: chr15-58306302;