rs4246323

Variant names:

• chr15-100902797-G-A
• rs4246323
• NM_000693.4:c.1068+2038G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-100902797-G-A
• chr15-100902797-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000693.4(ALDH1A3):​c.1068+2038G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 152,284 control chromosomes in the GnomAD database, including 1,417 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 0.096 (1417 hom., cov: 33)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.1068+2038G>A		intron_variant	Intron 9 of 12	ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2	c.747+2038G>A		intron_variant	Intron 6 of 9		NP_001280744.1
ALDH1A3-AS1	NR_135827.1	n.481-6731C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.1068+2038G>A		intron_variant	Intron 9 of 12	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14654 AN: 152166 Hom.: 1409 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0576

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.0965 AC: 14692 AN: 152284 Hom.: 1417 Cov.: 33 AF XY: 0.0974 AC XY: 7256 AN XY: 74470

African (AFR) AF: 0.252 AC: 10483 AN: 41526

American (AMR) AF: 0.0574 AC: 879 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3472

East Asian (EAS) AF: 0.0667 AC: 346 AN: 5186

South Asian (SAS) AF: 0.0544 AC: 263 AN: 4832

European-Finnish (FIN) AF: 0.0535 AC: 568 AN: 10616

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0249 AC: 1696 AN: 68032

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.0445 Hom.: 1764

Bravo AF: 0.103

Asia WGS AF: 0.0610 AC: 215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.74
PhyloP100		-0.35
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: rs4246323; hg19: chr15-101443002;