rs1806158

Variant names:

• chr11-31817240-C-G
• rs1806158
• ENST00000638914.3:c.-317+569G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-31817240-C-G
• chr11-31817240-C-T

Variant summary

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

The NM_001368919.2(PAX6):​c.-317+569G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,290 control chromosomes in the GnomAD database, including 4,158 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 0.22 (4158 hom., cov: 35)
• Consequence: PAX6 NM_001368919.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761
• Publications: 6 publications found

Genes affected

PAX6 (HGNC:8620): (paired box 6) This gene encodes paired box protein Pax-6, one of many human homologs of the Drosophila melanogaster gene prd. In addition to a conserved paired box domain, a hallmark feature of this gene family, the encoded protein also contains a homeobox domain. Both domains are known to bind DNA and function as regulators of gene transcription. Activity of this protein is key in the development of neural tissues, particularly the eye. This gene is regulated by multiple enhancers located up to hundreds of kilobases distant from this locus. Mutations in this gene or in the enhancer regions can cause ocular disorders such as aniridia and Peter's anomaly. Use of alternate promoters and alternative splicing results in multiple transcript variants encoding different isoforms. Interestingly, inclusion of a particular alternate coding exon has been shown to increase the length of the paired box domain and alter its DNA binding specificity. Consequently, isoforms that carry the shorter paired box domain regulate a different set of genes compared to the isoforms carrying the longer paired box domain. [provided by RefSeq, Mar 2019]

ENSG00000285283 (HGNC:):

PAUPAR (HGNC:49670): (PAX6 upstream antisense RNA) This gene is thought to produce a functional long non-coding RNA. Knockdown of this transcript results in genome-wide changes in gene expression, particularly of cell cyle genes, indicating a role in regulating differentiation. This transcript may bind to the promoter region of target genes and may also interact with the transcription factor Pax6 (paired box 6). [provided by RefSeq, Feb 2015]

PAX6-AS1 (HGNC:53448): (PAX6 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368919.2. 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
	PAX6	NM_001368919.2		c.-317+569G>C		intron	N/A	NP_001355848.1
	PAX6	NM_001258462.3		c.-317+569G>C		intron	N/A	NP_001245391.1	P26367-2
	PAX6	NM_001127612.3		c.-317+569G>C		intron	N/A	NP_001121084.1	P26367-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX6	ENST00000638914.3	TSL:1	c.-317+569G>C		intron	N/A	ENSP00000492315.2	P26367-2
	PAX6	ENST00000241001.13	TSL:1	c.-317+569G>C		intron	N/A	ENSP00000241001.8	P26367-1
	ENSG00000285283	ENST00000532942.5	TSL:2	c.101+601C>G		intron	N/A	ENSP00000436422.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33812 AN: 152172 Hom.: 4152 Cov.: 35

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.222 AC: 33854 AN: 152290 Hom.: 4158 Cov.: 35 AF XY: 0.221 AC XY: 16466 AN XY: 74472

African (AFR) AF: 0.318 AC: 13230 AN: 41552

American (AMR) AF: 0.211 AC: 3228 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1529 AN: 5170

South Asian (SAS) AF: 0.185 AC: 894 AN: 4832

European-Finnish (FIN) AF: 0.198 AC: 2104 AN: 10608

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11906 AN: 68028

Other (OTH) AF: 0.186 AC: 392 AN: 2112

Alfa AF: 0.104 Hom.: 158

Bravo AF: 0.228

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.74
DANN	Benign	0.57
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1806158; hg19: chr11-31838788;