rs2301254

Positions:

• chr11-32436129-A-G
• chr11-32436129-A-T

Variant summary

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

The NR_120548.1(WT1-AS):​n.329+283A>G 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 0.484 in 151,866 control chromosomes in the GnomAD database, including 19,618 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 0.48 (19618 hom., cov: 31)
• Consequence: WT1-AS NR_120548.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420

Genes affected

WT1-AS (HGNC:18135): (WT1 antisense RNA) This gene is located upstream of the Wilms tumor 1 (WT1) gene; these two genes are bi-directionally transcribed from the same promoter region. This gene is imprinted in kidney, with preferential expression from the paternal allele. Imprinting defects at chromosome 11p13 may contribute to tumorigenesis. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WT1-AS	NR_120548.1	n.329+283A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WT1-AS	ENST00000690579.1	n.225+283A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73399 AN: 151750 Hom.: 19570 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.484 AC: 73499 AN: 151866 Hom.: 19618 Cov.: 31 AF XY: 0.488 AC XY: 36226 AN XY: 74232

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.509

Alfa AF: 0.417 Hom.: 1793

Bravo AF: 0.502

Asia WGS AF: 0.711 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2301254; hg19: chr11-32457675;