rs9944290

chr15-100884530-G-Achr15-100884530-G-Cchr15-100884530-G-T

Variant summary

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

The NM_000693.4(ALDH1A3):c.100-737G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 150,128 control chromosomes in the GnomAD database, including 5,975 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 0.26 (5975 hom., cov: 31)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A3	NM_000693.4	c.100-737G>A		intron_variant		ENST00000329841.10
ALDH1A3	NM_001293815.2	c.100-737G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.100-737G>A		intron_variant		1	NM_000693.4	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39506 AN: 150056 Hom.: 5959 Cov.: 31

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.264 AC: 39562 AN: 150128 Hom.: 5975 Cov.: 31 AF XY: 0.267 AC XY: 19548 AN XY: 73128

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.248

Alfa AF: 0.194 Hom.: 4433

Bravo AF: 0.272

Asia WGS AF: 0.390 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.51
Dann	Benign	0.72

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: rs9944290; hg19: chr15-101424735;