rs12286701

Variant names:

• chr11-31841814-T-C
• rs12286701
• ENST00000532942.5:c.101+25175T>C

Variant summary

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

The ENST00000532942.5(ENSG00000285283):​c.101+25175T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,282 control chromosomes in the GnomAD database, including 802 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 0.078 (802 hom., cov: 32)
• Consequence: ENSG00000285283 ENST00000532942.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX6-AS1	NR_033971.1	n.74+25175T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285283	ENST00000532942.5	c.101+25175T>C		intron_variant	Intron 1 of 5	2		ENSP00000436422.1

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11825 AN: 152164 Hom.: 800 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0786

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0736

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

GnomAD4 genome AF: 0.0777 AC: 11838 AN: 152282 Hom.: 802 Cov.: 32 AF XY: 0.0777 AC XY: 5784 AN XY: 74468

African (AFR) AF: 0.173 AC: 7165 AN: 41530

American (AMR) AF: 0.0466 AC: 714 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0786 AC: 273 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5182

South Asian (SAS) AF: 0.0709 AC: 342 AN: 4824

European-Finnish (FIN) AF: 0.0393 AC: 417 AN: 10618

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0400 AC: 2720 AN: 68028

Other (OTH) AF: 0.0728 AC: 154 AN: 2114

Alfa AF: 0.0465 Hom.: 358

Bravo AF: 0.0807

Asia WGS AF: 0.0610 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		0.18
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: rs12286701; hg19: chr11-31863361;