rs677874

chr11-31869757-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.75-15537G>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 0.815 in 152,204 control chromosomes in the GnomAD database, including 51,139 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 0.82 (51139 hom., cov: 33)
• Consequence: PAX6-AS1 NR_033971.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX6-AS1	NR_033971.1	n.75-15537G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAUPAR	ENST00000644607.1	n.375-15537G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123998 AN: 152086 Hom.: 51090 Cov.: 33

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.815 AC: 124097 AN: 152204 Hom.: 51139 Cov.: 33 AF XY: 0.812 AC XY: 60439 AN XY: 74424

Gnomad4 AFR AF: 0.915

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.759

Alfa AF: 0.795 Hom.: 94446

Bravo AF: 0.810

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.4
Dann	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs677874; hg19: chr11-31891303;