11-31797787-C-G

Position:

• chr11-31797787-C-G

Variant summary

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

The NM_001368894.2(PAX6):​c.565+2904G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,120 control chromosomes in the GnomAD database, including 53,039 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 0.83 (53039 hom., cov: 31)
• Consequence: PAX6 NM_001368894.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX6	NM_001368894.2	c.565+2904G>C		intron_variant		ENST00000640368.2	NP_001355823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX6	ENST00000640368.2	c.565+2904G>C		intron_variant		5	NM_001368894.2	ENSP00000492024

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126792 AN: 152002 Hom.: 53002 Cov.: 31

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.834 AC: 126886 AN: 152120 Hom.: 53039 Cov.: 31 AF XY: 0.834 AC XY: 61974 AN XY: 74350

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.888

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.850

Alfa AF: 0.825 Hom.: 3022

Bravo AF: 0.829

Asia WGS AF: 0.782 AC: 2722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.5
DANN	Benign	0.57

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: rs592859; hg19: chr11-31819335;