15-100878477-C-T

Variant names:

• chr15-100878477-C-T
• rs3809523
• ENST00000561338.5:c.15+612C>T

Variant summary

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

The ENST00000561338.5(ALDH1A3):​c.15+612C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,180 control chromosomes in the GnomAD database, including 1,956 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 0.14 (1956 hom., cov: 33)
• Consequence: ALDH1A3 ENST00000561338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 2 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)

ENSG00000303930 (HGNC:):

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 = 0.4 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000561338.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	ENST00000561338.5	TSL:4	c.15+612C>T		intron	N/A	ENSP00000452789.1	H0YKF9
	ALDH1A3	ENST00000558568.1	TSL:2	n.502-6790C>T		intron	N/A
	ENSG00000303930	ENST00000798106.1		n.44+96G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20549 AN: 152062 Hom.: 1958 Cov.: 33

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.135 AC: 20552 AN: 152180 Hom.: 1956 Cov.: 33 AF XY: 0.136 AC XY: 10129 AN XY: 74378

African (AFR) AF: 0.0352 AC: 1461 AN: 41540

American (AMR) AF: 0.220 AC: 3362 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3470

East Asian (EAS) AF: 0.415 AC: 2142 AN: 5160

South Asian (SAS) AF: 0.193 AC: 930 AN: 4822

European-Finnish (FIN) AF: 0.107 AC: 1131 AN: 10594

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10652 AN: 67996

Other (OTH) AF: 0.163 AC: 343 AN: 2110

Alfa AF: 0.155 Hom.: 1182

Bravo AF: 0.141

Asia WGS AF: 0.288 AC: 999 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	5.7
DANN	Benign	0.78
PhyloP100		0.083

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3809523;

hg19: chr15-101418682;