11-31883988-C-T

Variant names:

• chr11-31883988-C-T
• rs652722
• ENST00000532942.5:c.101+67349C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000532942.5(ENSG00000285283):​c.101+67349C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,130 control chromosomes in the GnomAD database, including 8,277 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 0.32 (8277 hom., cov: 33)
• Consequence: ENSG00000285283 ENST00000532942.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 23 publications found

Genes affected

ENSG00000285283 (HGNC:):

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:53448): (PAX6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX6-AS1	NR_033971.1	n.75-1306C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285283	ENST00000532942.5	c.101+67349C>T		intron_variant	Intron 1 of 5	2		ENSP00000436422.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48226 AN: 152010 Hom.: 8265 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.317 AC: 48269 AN: 152130 Hom.: 8277 Cov.: 33 AF XY: 0.317 AC XY: 23556 AN XY: 74386

African (AFR) AF: 0.443 AC: 18371 AN: 41494

American (AMR) AF: 0.324 AC: 4958 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3466

East Asian (EAS) AF: 0.390 AC: 2013 AN: 5166

South Asian (SAS) AF: 0.225 AC: 1084 AN: 4820

European-Finnish (FIN) AF: 0.236 AC: 2498 AN: 10584

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17355 AN: 67994

Other (OTH) AF: 0.295 AC: 623 AN: 2112

Alfa AF: 0.278 Hom.: 26429

Bravo AF: 0.326

Asia WGS AF: 0.290 AC: 1009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.49
DANN	Benign	0.60
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs652722; hg19: chr11-31905534;