15-100884530-G-A

Variant names:

• chr15-100884530-G-A
• rs9944290
• NM_000693.4:c.100-737G>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.100-737G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 150,128 control chromosomes in the GnomAD database, including 5,975 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 0.26 (5975 hom., cov: 31)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 6 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 Gene-Disease associations (from GenCC):

• isolated anophthalmia-microphthalmia syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• isolated microphthalmia 8

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 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.100-737G>A		intron	N/A	NP_000684.2	P47895
	ALDH1A3	NM_001293815.2		c.100-737G>A		intron	N/A	NP_001280744.1	H0Y2X5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	ENST00000329841.10	TSL:1 MANE Select	c.100-737G>A		intron	N/A	ENSP00000332256.5	P47895
	ALDH1A3	ENST00000346623.6	TSL:1	c.100-737G>A		intron	N/A	ENSP00000343294.6	H0Y2X5
	ALDH1A3	ENST00000560555.1	TSL:1	n.160-737G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39506 AN: 150056 Hom.: 5959 Cov.: 31

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.264 AC: 39562 AN: 150128 Hom.: 5975 Cov.: 31 AF XY: 0.267 AC XY: 19548 AN XY: 73128

African (AFR) AF: 0.377 AC: 15434 AN: 40976

American (AMR) AF: 0.281 AC: 4246 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 541 AN: 3456

East Asian (EAS) AF: 0.570 AC: 2895 AN: 5078

South Asian (SAS) AF: 0.192 AC: 911 AN: 4750

European-Finnish (FIN) AF: 0.267 AC: 2617 AN: 9788

Middle Eastern (MID) AF: 0.141 AC: 40 AN: 284

European-Non Finnish (NFE) AF: 0.182 AC: 12295 AN: 67696

Other (OTH) AF: 0.248 AC: 517 AN: 2088

Alfa AF: 0.205 Hom.: 7034

Bravo AF: 0.272

Asia WGS AF: 0.390 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.72
PhyloP100		-0.12
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: rs9944290; hg19: chr15-101424735;