rs6508

chr11-32438918-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_120548.1(WT1-AS):n.329+3072G>A 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 0.0978 in 534,676 control chromosomes in the GnomAD database, including 5,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (3318 hom., cov: 33)
  • Exomes 𝑓: 0.076 (1736 hom.)
• Consequence: WT1-AS NR_120548.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.315

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-32438918-G-A is Benign according to our data. Variant chr11-32438918-G-A is described in ClinVar as [Benign]. Clinvar id is 1166184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WT1-AS	NR_120548.1	n.329+3072G>A		intron_variant, non_coding_transcript_variant
WT1-AS	NR_120546.1	n.1873G>A		non_coding_transcript_exon_variant	2/2
WT1-AS	NR_120547.1	n.1531G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WT1-AS	ENST00000690579.1	n.225+3072G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23364 AN: 152114 Hom.: 3308 Cov.: 33

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0905

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.0696

Gnomad OTH AF: 0.132

GnomAD3 exomes AF: 0.0828 AC: 20820 AN: 251372 Hom.: 1748 AF XY: 0.0774 AC XY: 10514 AN XY: 135878

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.0551

Gnomad ASJ exome AF: 0.0840

Gnomad EAS exome AF: 0.00261

Gnomad SAS exome AF: 0.0758

Gnomad FIN exome AF: 0.0532

Gnomad NFE exome AF: 0.0689

Gnomad OTH exome AF: 0.0774

GnomAD4 exome AF: 0.0756 AC: 28901 AN: 382444 Hom.: 1736 Cov.: 0 AF XY: 0.0743 AC XY: 16174 AN XY: 217716

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.0563

Gnomad4 ASJ exome AF: 0.0837

Gnomad4 EAS exome AF: 0.00486

Gnomad4 SAS exome AF: 0.0801

Gnomad4 FIN exome AF: 0.0529

Gnomad4 NFE exome AF: 0.0679

Gnomad4 OTH exome AF: 0.0836

GnomAD4 genome AF: 0.154 AC: 23415 AN: 152232 Hom.: 3318 Cov.: 33 AF XY: 0.150 AC XY: 11183 AN XY: 74444

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.0904

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.0683

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.0696

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0950 Hom.: 1604

Bravo AF: 0.165

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

11p partial monosomy syndrome;C0950121:Drash syndrome;C0950122:Frasier syndrome;CN033288:Wilms tumor 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.3
Dann	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6508; hg19: chr11-32460464;