rs117848117

Variant names:

• chr10-120871300-G-A
• rs117848117
• NM_018117.12:c.1425G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018117.12(WDR11):​c.1425G>A​(p.Pro475Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,613,770 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (17 hom.)
• Consequence: WDR11 NM_018117.12 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.62

Genes affected

WDR11 (HGNC:13831): (WD repeat domain 11) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is located in the chromosome 10q25-26 region, which is frequently deleted in gliomas and tumors of other tissues, and is disrupted by the t(10;19) translocation rearrangement in glioblastoma cells. The gene location suggests that it is a candidate gene for the tumor suppressor locus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-120871300-G-A is Benign according to our data. Variant chr10-120871300-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 437271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-120871300-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.62 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00228 (346/151902) while in subpopulation NFE AF= 0.00374 (254/67958). AF 95% confidence interval is 0.00336. There are 0 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 346 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12	c.1425G>A	p.Pro475Pro	synonymous_variant	Exon 10 of 29	ENST00000263461.11	NP_060587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000263461.11	c.1425G>A	p.Pro475Pro	synonymous_variant	Exon 10 of 29	1	NM_018117.12	ENSP00000263461.5
WDR11	ENST00000497136.6	n.544G>A		non_coding_transcript_exon_variant	Exon 8 of 26	1		ENSP00000474595.1
WDR11	ENST00000605543.5	n.232G>A		non_coding_transcript_exon_variant	Exon 3 of 22	2		ENSP00000475076.1

Frequencies

GnomAD3 genomes AF: 0.00228 AC: 346 AN: 151792 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000605

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000853

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00468

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00374

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00275 AC: 692 AN: 251464 Hom.: 4 AF XY: 0.00263 AC XY: 357 AN XY: 135914

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00374

Gnomad NFE exome AF: 0.00513

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00310 AC: 4531 AN: 1461868 Hom.: 17 Cov.: 32 AF XY: 0.00297 AC XY: 2160 AN XY: 727234

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000313

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00425

Gnomad4 NFE exome AF: 0.00372

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.00228 AC: 346 AN: 151902 Hom.: 0 Cov.: 32 AF XY: 0.00220 AC XY: 163 AN XY: 74232

Gnomad4 AFR AF: 0.000603

Gnomad4 AMR AF: 0.000852

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00468

Gnomad4 NFE AF: 0.00374

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00305 Hom.: 0

Bravo AF: 0.00181

EpiCase AF: 0.00278

EpiControl AF: 0.00284

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 12, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

May 12, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs117848117; hg19: chr10-122630812; COSMIC: COSV54791774;