rs537446654

Variant names:

• chr11-31818219-G-A
• rs537446654
• ENST00000532942.5:c.101+1580G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000532942.5(ENSG00000285283):​c.101+1580G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 152,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0023 (0 hom., cov: 34)
• Consequence: ENSG00000285283 ENST00000532942.5 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.559
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX6-AS1	NR_033971.1	n.74+1580G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285283	ENST00000532942.5	c.101+1580G>A		intron_variant	Intron 1 of 5	2		ENSP00000436422.1

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 352 AN: 152190 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000719

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00970

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00298

Gnomad OTH AF: 0.000957

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

GnomAD4 genome AF: 0.00232 AC: 353 AN: 152308 Hom.: 0 Cov.: 34 AF XY: 0.00258 AC XY: 192 AN XY: 74470

African (AFR) AF: 0.000794 AC: 33 AN: 41562

American (AMR) AF: 0.000718 AC: 11 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00970 AC: 103 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00300 AC: 204 AN: 68032

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00355 Hom.: 0

Bravo AF: 0.00153

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Aniridia 1 Uncertain:1

Aug 01, 2018

Genetics Department, University Hospital of Toulouse

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.25
DANN	Benign	0.79
PhyloP100		-0.56
PromoterAI		0.00030	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs537446654; hg19: chr11-31839767;