chr15-100900009-G-A

Variant names:

• chr15-100900009-G-A
• rs4646672
• NM_000693.4:c.884-566G>A

Variant summary

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

The NM_000693.4(ALDH1A3):​c.884-566G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 152,184 control chromosomes in the GnomAD database, including 1,280 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 0.092 (1280 hom., cov: 33)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.884-566G>A		intron_variant	Intron 8 of 12	ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2	c.563-566G>A		intron_variant	Intron 5 of 9		NP_001280744.1
ALDH1A3-AS1	NR_135827.1	n.481-3943C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.884-566G>A		intron_variant	Intron 8 of 12	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13983 AN: 152066 Hom.: 1273 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0879

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

GnomAD4 genome AF: 0.0921 AC: 14011 AN: 152184 Hom.: 1280 Cov.: 33 AF XY: 0.0931 AC XY: 6923 AN XY: 74400

African (AFR) AF: 0.238 AC: 9860 AN: 41484

American (AMR) AF: 0.0559 AC: 855 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3470

East Asian (EAS) AF: 0.0658 AC: 341 AN: 5186

South Asian (SAS) AF: 0.0539 AC: 260 AN: 4820

European-Finnish (FIN) AF: 0.0535 AC: 566 AN: 10584

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

European-Non Finnish (NFE) AF: 0.0248 AC: 1685 AN: 68020

Other (OTH) AF: 0.0874 AC: 185 AN: 2116

Alfa AF: 0.0396 Hom.: 479

Bravo AF: 0.0993

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.024
DANN	Benign	0.83
PhyloP100		-0.88
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: rs4646672; hg19: chr15-101440214;