rs71873106

Variant names:

• chr11-32430545-AGC-A
• rs71873106
• ENST00000379079.8:c.-8_-7delGC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001198551.2(WT1):​c.-8_-7delGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,608,994 control chromosomes in the GnomAD database, including 225 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (114 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (111 hom.)
• Consequence: WT1 NM_001198551.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.880
• Publications: 0 publications found

Genes affected

WT1 (HGNC:12796): (WT1 transcription factor) This gene encodes a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a small subset of patients with Wilms tumor. This gene exhibits complex tissue-specific and polymorphic imprinting pattern, with biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues. Multiple transcript variants have been described. In several variants, there is evidence for the use of a non-AUG (CUG) translation initiation codon upstream of, and in-frame with the first AUG. Authors of PMID:7926762 also provide evidence that WT1 mRNA undergoes RNA editing in human and rat, and that this process is tissue-restricted and developmentally regulated. [provided by RefSeq, Mar 2015]

WT1 Gene-Disease associations (from GenCC):

• Denys-Drash syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, G2P
• Wilms tumor 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Frasier syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 11-32430545-AGC-A is Benign according to our data. Variant chr11-32430545-AGC-A is described in ClinVar as Benign. ClinVar VariationId is 257619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198551.2. 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
	WT1	NM_024426.6	MANE Select	c.662-1928_662-1927delGC		intron	N/A	NP_077744.4
	WT1	NM_001198551.2		c.-8_-7delGC		5_prime_UTR	Exon 1 of 10	NP_001185480.1
	WT1	NM_001198552.2		c.-8_-7delGC		5_prime_UTR	Exon 1 of 9	NP_001185481.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WT1	ENST00000379079.8	TSL:1	c.-8_-7delGC		5_prime_UTR	Exon 1 of 10	ENSP00000368370.2
	WT1	ENST00000452863.10	TSL:1 MANE Select	c.662-1928_662-1927delGC		intron	N/A	ENSP00000415516.5
	WT1	ENST00000639563.4	TSL:1	c.662-1928_662-1927delGC		intron	N/A	ENSP00000492269.3

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3139 AN: 149700 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0742

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.000195

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.0224

GnomAD2 exomes AF: 0.00476 AC: 1138 AN: 239094 AF XY: 0.00356

Gnomad AFR exome AF: 0.0702

Gnomad AMR exome AF: 0.00344

Gnomad ASJ exome AF: 0.000304

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000938

Gnomad NFE exome AF: 0.000198

Gnomad OTH exome AF: 0.00271

GnomAD4 exome AF: 0.00221 AC: 3232 AN: 1459184 Hom.: 111 AF XY: 0.00196 AC XY: 1420 AN XY: 725746

African (AFR) AF: 0.0772 AC: 2578 AN: 33406

American (AMR) AF: 0.00426 AC: 190 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.000128 AC: 11 AN: 85824

European-Finnish (FIN) AF: 0.0000768 AC: 4 AN: 52082

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5764

European-Non Finnish (NFE) AF: 0.000143 AC: 159 AN: 1111442

Other (OTH) AF: 0.00448 AC: 270 AN: 60296

GnomAD4 genome AF: 0.0210 AC: 3139 AN: 149810 Hom.: 114 Cov.: 32 AF XY: 0.0206 AC XY: 1505 AN XY: 73190

African (AFR) AF: 0.0741 AC: 2979 AN: 40224

American (AMR) AF: 0.00627 AC: 94 AN: 14984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 4992

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4776

European-Finnish (FIN) AF: 0.000195 AC: 2 AN: 10260

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000236 AC: 16 AN: 67824

Other (OTH) AF: 0.0221 AC: 46 AN: 2078

Alfa AF: 0.0102 Hom.: 8

Bravo AF: 0.0236

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Drash syndrome (1)
-	-	1	Frasier syndrome (1)
-	-	1	Meacham syndrome (1)
-	-	1	Nephrotic syndrome, type 4 (1)
-	-	1	Wilms tumor 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.88
Mutation Taster		=297/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs71873106; hg19: chr11-32452091; COSMIC: COSV104651942;