11-31856454-T-C

Variant names:

• chr11-31856454-T-C
• rs761453
• ENST00000532942.5:c.101+39815T>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+39815T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,108 control chromosomes in the GnomAD database, including 52,295 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 (52295 hom., cov: 31)
• Consequence: ENSG00000285283 ENST00000532942.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000532942.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX6-AS1	NR_033971.1		n.75-28840T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285283	ENST00000532942.5	TSL:2	c.101+39815T>C		intron	N/A	ENSP00000436422.1
	PAUPAR	ENST00000506388.2	TSL:1	n.75-28840T>C		intron	N/A
	ENSG00000285283	ENST00000530348.5	TSL:4	c.-245+43957T>C		intron	N/A	ENSP00000436482.1	E9PP27

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125288 AN: 151992 Hom.: 52244 Cov.: 31

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.824 AC: 125390 AN: 152108 Hom.: 52295 Cov.: 31 AF XY: 0.823 AC XY: 61201 AN XY: 74388

African (AFR) AF: 0.932 AC: 38685 AN: 41506

American (AMR) AF: 0.737 AC: 11270 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2663 AN: 3468

East Asian (EAS) AF: 0.580 AC: 2987 AN: 5152

South Asian (SAS) AF: 0.711 AC: 3436 AN: 4832

European-Finnish (FIN) AF: 0.870 AC: 9204 AN: 10582

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54567 AN: 67966

Other (OTH) AF: 0.761 AC: 1605 AN: 2108

Alfa AF: 0.797 Hom.: 78582

Bravo AF: 0.815

Asia WGS AF: 0.634 AC: 2207 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.1
DANN	Benign	0.55
PhyloP100		-0.011
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: rs761453; hg19: chr11-31878000;