Variant rs3026393 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001368894.2(PAX6):c.1225+43T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,612,374 control chromosomes in the GnomAD database, including 204,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.45 ( 15850 hom., cov: 32)

Exomes 𝑓: 0.51 ( 189093 hom. )

Consequence

PAX6
NM_001368894.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.471

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-31790667-A-C is Benign according to our data. Variant chr11-31790667-A-C is described in ClinVar as [Benign]. Clinvar id is 1283019.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-31790667-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX6	NM_001368894.2 linkuse as main transcript	c.1225+43T>G		intron_variant		ENST00000640368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX6	ENST00000640368.2 linkuse as main transcript	c.1225+43T>G		intron_variant		5	NM_001368894.2		P26367-2

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67978

AN:

151954

Hom.:

15834

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.483

Gnomad EAS

AF:

0.456

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.477

GnomAD3 exomes

AF:

0.480

AC:

120157

AN:

250416

Hom.:

29703

AF XY:

0.494

AC XY:

66867

AN XY:

135360

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.347

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.447

Gnomad SAS exome

AF:

0.599

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.517

Gnomad OTH exome

AF:

0.489

GnomAD4 exome

AF:

0.506

AC:

738371

AN:

1460302

Hom.:

189093

Cov.:

AF XY:

0.510

AC XY:

370788

AN XY:

726452

show subpopulations

Gnomad4 AFR exome

AF:

0.315

Gnomad4 AMR exome

AF:

0.356

Gnomad4 ASJ exome

AF:

0.471

Gnomad4 EAS exome

AF:

0.459

Gnomad4 SAS exome

AF:

0.597

Gnomad4 FIN exome

AF:

0.473

Gnomad4 NFE exome

AF:

0.515

Gnomad4 OTH exome

AF:

0.488

GnomAD4 genome

AF:

0.447

AC:

68015

AN:

152072

Hom.:

15850

Cov.:

AF XY:

0.447

AC XY:

33234

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.412

Gnomad4 ASJ

AF:

0.483

Gnomad4 EAS

AF:

0.456

Gnomad4 SAS

AF:

0.588

Gnomad4 FIN

AF:

0.471

Gnomad4 NFE

AF:

0.516

Gnomad4 OTH

AF:

0.484

Alfa

AF:

0.424

Hom.:

3105

Bravo

AF:

0.433

Asia WGS

AF:

0.507

AC:

1766

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.6

DANN

Benign

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over