rs1802603

Positions:

• chr15-100916579-G-A

Variant summary

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

The NM_000693.4(ALDH1A3):​c.*1806G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,246 control chromosomes in the GnomAD database, including 1,763 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 0.10 (1763 hom., cov: 33)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: ALDH1A3 NM_000693.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

Genes affected

ALDH1A3 (HGNC:409): (aldehyde dehydrogenase 1 family member A3) This gene encodes an aldehyde dehydrogenase enzyme that uses retinal as a substrate. Mutations in this gene have been associated with microphthalmia, isolated 8, and expression changes have also been detected in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ALDH1A3-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.*1806G>A		3_prime_UTR_variant	13/13	ENST00000329841.10	NP_000684.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.*1806G>A		3_prime_UTR_variant	13/13	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15927 AN: 152096 Hom.: 1754 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.0546

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0251

Gnomad OTH AF: 0.0963

GnomAD4 exome AF: 0.0625 AC: 2 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.0417 AC XY: 1 AN XY: 24

Gnomad4 FIN exome AF: 0.0625

GnomAD4 genome AF: 0.105 AC: 15966 AN: 152214 Hom.: 1763 Cov.: 33 AF XY: 0.105 AC XY: 7848 AN XY: 74432

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.0623

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.0684

Gnomad4 SAS AF: 0.0542

Gnomad4 FIN AF: 0.0535

Gnomad4 NFE AF: 0.0252

Gnomad4 OTH AF: 0.0957

Alfa AF: 0.0450 Hom.: 670

Bravo AF: 0.112

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.52

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: rs1802603; hg19: chr15-101456784;