rs3803426

Positions:

• chr15-100914981-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000693.4(ALDH1A3):​c.*208C>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 0.042 in 571,442 control chromosomes in the GnomAD database, including 904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (480 hom., cov: 33)
  • Exomes 𝑓: 0.035 (424 hom.)
• Consequence: ALDH1A3 NM_000693.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.465

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 15-100914981-C-T is Benign according to our data. Variant chr15-100914981-C-T is described in ClinVar as [Benign]. Clinvar id is 1287624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.*208C>T		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.*208C>T		3_prime_UTR_variant	13/13	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9348 AN: 152182 Hom.: 480 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0385

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.0492

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0559

GnomAD4 exome AF: 0.0349 AC: 14647 AN: 419142 Hom.: 424 Cov.: 4 AF XY: 0.0350 AC XY: 7710 AN XY: 219984

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.0278

Gnomad4 ASJ exome AF: 0.0559

Gnomad4 EAS exome AF: 0.0743

Gnomad4 SAS exome AF: 0.0459

Gnomad4 FIN exome AF: 0.0429

Gnomad4 NFE exome AF: 0.0215

Gnomad4 OTH exome AF: 0.0409

GnomAD4 genome AF: 0.0615 AC: 9361 AN: 152300 Hom.: 480 Cov.: 33 AF XY: 0.0630 AC XY: 4695 AN XY: 74476

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0384

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.0671

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.0523

Gnomad4 NFE AF: 0.0206

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0288 Hom.: 231

Bravo AF: 0.0634

Asia WGS AF: 0.0530 AC: 186 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.6
DANN	Benign	0.82

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: rs3803426; hg19: chr15-101455186;