rs224603

Variant names:

• chr11-31956465-G-C
• rs224603
• ENST00000532942.5:c.101+139826G>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+139826G>C variant causes a intron 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: ENSG00000285283 ENST00000532942.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285283	ENST00000532942.5	TSL:2	c.101+139826G>C		intron	N/A	ENSP00000436422.1
	ENSG00000285283	ENST00000530348.5	TSL:4	c.-244-140679G>C		intron	N/A	ENSP00000436482.1	E9PP27
	PAUPAR	ENST00000642818.1		n.78-2250G>C		intron	N/A

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

African (AFR) AF: 0.546 AC: 22641 AN: 41458

American (AMR) AF: 0.544 AC: 8319 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2115 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1838 AN: 5146

South Asian (SAS) AF: 0.727 AC: 3486 AN: 4798

European-Finnish (FIN) AF: 0.740 AC: 7837 AN: 10584

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48452 AN: 67966

Other (OTH) AF: 0.647 AC: 1365 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.24
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs224603;

hg19: chr11-31978011;