11-31819578-G-T

Variant summary

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

The NR_033971.1(PAX6-AS1):n.74+2939G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,250 control chromosomes in the GnomAD database, including 2,005 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 0.15 (2005 hom., cov: 33)
• Consequence: PAX6-AS1 NR_033971.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX6-AS1	NR_033971.1	n.74+2939G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAUPAR	ENST00000644607.1	n.374+2939G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22838 AN: 152132 Hom.: 2007 Cov.: 33

Gnomad AFR AF: 0.0678

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.150 AC: 22849 AN: 152250 Hom.: 2005 Cov.: 33 AF XY: 0.152 AC XY: 11339 AN XY: 74424

Gnomad4 AFR AF: 0.0679

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.132

Alfa AF: 0.101 Hom.: 244

Bravo AF: 0.145

Asia WGS AF: 0.208 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.30
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1806155; hg19: chr11-31841125;