11-31811994-C-G

Position:

• chr11-31811994-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001368915.2(PAX6):​c.-503G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,540 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 0.18 (2572 hom., cov: 32)
  • Exomes 𝑓: 0.15 (4 hom.)
• Consequence: PAX6 NM_001368915.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812

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]

PAX6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX6	NM_001368915.2	c.-503G>C		5_prime_UTR_variant	1/12		NP_001355844.1
PAX6	NM_001368887.2	c.-503G>C		5_prime_UTR_variant	1/13		NP_001355816.1
PAX6	NM_001368919.2	c.-316-979G>C		intron_variant			NP_001355848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX6	ENST00000638914.3	c.-316-979G>C		intron_variant		1		ENSP00000492315.2
PAX6	ENST00000639409.1	c.-317+99G>C		intron_variant		1		ENSP00000492476.1
PAX6	ENST00000640975.1	c.-317+155G>C		intron_variant		1		ENSP00000491872.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26941 AN: 152118 Hom.: 2570 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.155 AC: 47 AN: 304 Hom.: 4 Cov.: 0 AF XY: 0.161 AC XY: 38 AN XY: 236

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.177 AC: 26974 AN: 152236 Hom.: 2572 Cov.: 32 AF XY: 0.177 AC XY: 13177 AN XY: 74430

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0770 Hom.: 100

Bravo AF: 0.183

Asia WGS AF: 0.220 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071164; hg19: chr11-31833542;