rs224603

chr11-31956465-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000644607.1(PAUPAR):n.887-43260G>C 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 0.638 in 152,030 control chromosomes in the GnomAD database, including 31,706 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 0.64 (31706 hom., cov: 31)
• Consequence: PAUPAR ENST00000644607.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAUPAR	ENST00000644607.1	n.887-43260G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96916 AN: 151912 Hom.: 31694 Cov.: 31

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.638 AC: 96968 AN: 152030 Hom.: 31706 Cov.: 31 AF XY: 0.635 AC XY: 47207 AN XY: 74316

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.647

Alfa AF: 0.664 Hom.: 4195

Bravo AF: 0.615

Asia WGS AF: 0.563 AC: 1959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.0
Dann	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs224603; hg19: chr11-31978011;