rs4246328

Positions:

• chr15-100906065-G-A
• chr15-100906065-G-C

Variant summary

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

The NM_000693.4(ALDH1A3):​c.1233+378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,978 control chromosomes in the GnomAD database, including 17,068 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 0.45 (17068 hom., cov: 32)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A3	NM_000693.4	c.1233+378G>A		intron_variant		ENST00000329841.10
ALDH1A3-AS1	NR_135827.1	n.481-9999C>T		intron_variant, non_coding_transcript_variant
ALDH1A3	NM_001293815.2	c.912+378G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.1233+378G>A		intron_variant		1	NM_000693.4	P1
ALDH1A3-AS1	ENST00000656756.1	n.589-9999C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68662 AN: 151860 Hom.: 17058 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.452 AC: 68701 AN: 151978 Hom.: 17068 Cov.: 32 AF XY: 0.457 AC XY: 33968 AN XY: 74258

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.464

Alfa AF: 0.517 Hom.: 11744

Bravo AF: 0.432

Asia WGS AF: 0.673 AC: 2341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
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: rs4246328; hg19: chr15-101446270;