rs12914598

Variant names:

• chr15-100910274-G-A
• rs12914598
• NM_000693.4:c.1466+1792G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-100910274-G-A
• chr15-100910274-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.1466+1792G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,246 control chromosomes in the GnomAD database, including 2,576 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 0.16 (2576 hom., cov: 34)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.814
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	NM_000693.4	MANE Select	c.1466+1792G>A		intron	N/A	NP_000684.2	P47895
	ALDH1A3	NM_001293815.2		c.1145+1792G>A		intron	N/A	NP_001280744.1	H0Y2X5
	ALDH1A3-AS1	NR_135827.1		n.480+8530C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	ENST00000329841.10	TSL:1 MANE Select	c.1466+1792G>A		intron	N/A	ENSP00000332256.5	P47895
	ALDH1A3	ENST00000346623.6	TSL:1	c.1145+1792G>A		intron	N/A	ENSP00000343294.6	H0Y2X5
	ALDH1A3	ENST00000856095.1		c.1565+1792G>A		intron	N/A	ENSP00000526154.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24552 AN: 152128 Hom.: 2574 Cov.: 34

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.161 AC: 24550 AN: 152246 Hom.: 2576 Cov.: 34 AF XY: 0.165 AC XY: 12277 AN XY: 74430

African (AFR) AF: 0.0515 AC: 2139 AN: 41556

American (AMR) AF: 0.224 AC: 3423 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 666 AN: 3472

East Asian (EAS) AF: 0.442 AC: 2286 AN: 5170

South Asian (SAS) AF: 0.168 AC: 809 AN: 4828

European-Finnish (FIN) AF: 0.198 AC: 2093 AN: 10594

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12686 AN: 68004

Other (OTH) AF: 0.161 AC: 341 AN: 2114

Alfa AF: 0.178 Hom.: 4005

Bravo AF: 0.161

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.64
PhyloP100		0.81
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: rs12914598; hg19: chr15-101450479;