rs4246328

Variant names:

• chr15-100906065-G-A
• rs4246328
• NM_000693.4:c.1233+378G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000693.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	NM_000693.4	MANE Select	c.1233+378G>A		intron	N/A	NP_000684.2
	ALDH1A3	NM_001293815.2		c.912+378G>A		intron	N/A	NP_001280744.1
	ALDH1A3-AS1	NR_135827.1		n.481-9999C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	ENST00000329841.10	TSL:1 MANE Select	c.1233+378G>A		intron	N/A	ENSP00000332256.5
	ALDH1A3	ENST00000346623.6	TSL:1	c.912+378G>A		intron	N/A	ENSP00000343294.6
	ALDH1A3	ENST00000558869.1	TSL:4	n.476+378G>A		intron	N/A

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

African (AFR) AF: 0.233 AC: 9665 AN: 41448

American (AMR) AF: 0.456 AC: 6973 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1908 AN: 3468

East Asian (EAS) AF: 0.653 AC: 3372 AN: 5164

South Asian (SAS) AF: 0.662 AC: 3180 AN: 4806

European-Finnish (FIN) AF: 0.549 AC: 5795 AN: 10554

Middle Eastern (MID) AF: 0.486 AC: 141 AN: 290

European-Non Finnish (NFE) AF: 0.532 AC: 36125 AN: 67948

Other (OTH) AF: 0.464 AC: 979 AN: 2112

Alfa AF: 0.511 Hom.: 15489

Bravo AF: 0.432

Asia WGS AF: 0.673 AC: 2341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.52
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4246328; hg19: chr15-101446270;