rs1045154

Variant names:

• chr10-120909092-G-A
• rs1045154
• ENST00000497136.6:n.*3327G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000497136.6(WDR11):​n.*3327G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 264,386 control chromosomes in the GnomAD database, including 14,074 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 0.31 (7645 hom., cov: 33)
  • Exomes 𝑓: 0.33 (6429 hom.)
• Consequence: WDR11 ENST00000497136.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879
• Publications: 13 publications found

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]

WDR11 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 14 with or without anosmia

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
• intellectual developmental disorder, autosomal recessive 78

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypogonadotropic hypogonadism

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC105378519 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000497136.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR11	NM_018117.12	MANE Select	c.*379G>A		3_prime_UTR	Exon 29 of 29	NP_060587.8

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR11	ENST00000497136.6	TSL:1	n.*3327G>A		non_coding_transcript_exon	Exon 26 of 26	ENSP00000474595.1
	WDR11	ENST00000605543.5	TSL:2	n.*2573G>A		non_coding_transcript_exon	Exon 22 of 22	ENSP00000475076.1
	WDR11	ENST00000263461.11	TSL:1 MANE Select	c.*379G>A		3_prime_UTR	Exon 29 of 29	ENSP00000263461.5

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47256 AN: 151974 Hom.: 7639 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.329 AC: 36948 AN: 112294 Hom.: 6429 Cov.: 0 AF XY: 0.329 AC XY: 19470 AN XY: 59182

African (AFR) AF: 0.196 AC: 701 AN: 3580

American (AMR) AF: 0.468 AC: 2170 AN: 4634

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1138 AN: 2836

East Asian (EAS) AF: 0.404 AC: 2271 AN: 5624

South Asian (SAS) AF: 0.313 AC: 5165 AN: 16484

European-Finnish (FIN) AF: 0.290 AC: 1541 AN: 5312

Middle Eastern (MID) AF: 0.307 AC: 130 AN: 424

European-Non Finnish (NFE) AF: 0.324 AC: 21901 AN: 67524

Other (OTH) AF: 0.329 AC: 1931 AN: 5876

GnomAD4 genome AF: 0.311 AC: 47284 AN: 152092 Hom.: 7645 Cov.: 33 AF XY: 0.310 AC XY: 23054 AN XY: 74334

African (AFR) AF: 0.214 AC: 8859 AN: 41490

American (AMR) AF: 0.415 AC: 6346 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3470

East Asian (EAS) AF: 0.417 AC: 2162 AN: 5182

South Asian (SAS) AF: 0.331 AC: 1596 AN: 4824

European-Finnish (FIN) AF: 0.283 AC: 2982 AN: 10550

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22891 AN: 67972

Other (OTH) AF: 0.317 AC: 671 AN: 2114

Alfa AF: 0.335 Hom.: 10541

Bravo AF: 0.318

Asia WGS AF: 0.375 AC: 1305 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.8
DANN	Benign	0.61
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1045154; hg19: chr10-122668604;