15-100916578-C-T

Position:

• chr15-100916578-C-T

Variant summary

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

The NM_000693.4(ALDH1A3):​c.*1805C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,208 control chromosomes in the GnomAD database, including 2,604 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 0.16 (2602 hom., cov: 33)
  • Exomes 𝑓: 0.27 (2 hom.)
• Consequence: ALDH1A3 NM_000693.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456

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:55416): (ALDH1A3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.*1805C>T		3_prime_UTR_variant	13/13	ENST00000329841.10	NP_000684.2
ALDH1A3-AS1	NR_135827.1	n.480+2226G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.*1805C>T		3_prime_UTR_variant	13/13	1	NM_000693.4	ENSP00000332256	P1
ALDH1A3-AS1	ENST00000656756.1	n.588+2226G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24768 AN: 152060 Hom.: 2600 Cov.: 33

Gnomad AFR AF: 0.0523

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.267 AC: 8 AN: 30 Hom.: 2 Cov.: 0 AF XY: 0.292 AC XY: 7 AN XY: 24

Gnomad4 FIN exome AF: 0.267

GnomAD4 genome AF: 0.163 AC: 24767 AN: 152178 Hom.: 2602 Cov.: 33 AF XY: 0.166 AC XY: 12378 AN XY: 74380

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.164

Alfa AF: 0.183 Hom.: 4301

Bravo AF: 0.163

Asia WGS AF: 0.288 AC: 999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.61

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: rs7045; hg19: chr15-101456783;