chr15-100916112-G-A

Position:

• chr15-100916112-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.*1339G>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 0.171 in 152,146 control chromosomes in the GnomAD database, including 2,717 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 0.17 (2717 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ALDH1A3 NM_000693.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.*1339G>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.*1339G>A		3_prime_UTR_variant	13/13	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26001 AN: 152026 Hom.: 2715 Cov.: 33

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.171 AC: 26017 AN: 152144 Hom.: 2717 Cov.: 33 AF XY: 0.174 AC XY: 12977 AN XY: 74394

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.167

Alfa AF: 0.184 Hom.: 3627

Bravo AF: 0.172

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.55

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: rs14226; hg19: chr15-101456317;