ENST00000456120.6:n.21C>T

Variant names:

• chr10-120851124-G-A
• rs74158326
• ENST00000456120.6:n.21C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000456120.6(WDR11-DT):​n.21C>T 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 0.00352 in 497,624 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (18 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (5 hom.)
• Consequence: WDR11-DT ENST00000456120.6 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0950
• Publications: 0 publications found

Genes affected

WDR11-DT (HGNC:27437): (WDR11 divergent transcript)

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 10-120851124-G-A is Benign according to our data. Variant chr10-120851124-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1190555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00895 (1363/152334) while in subpopulation AFR AF = 0.0314 (1304/41570). AF 95% confidence interval is 0.03. There are 18 homozygotes in GnomAd4. There are 652 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000456120.6. 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
	WDR11-DT	NR_033850.1		n.56C>T		non_coding_transcript_exon	Exon 1 of 3
	WDR11	NM_018117.12	MANE Select	c.-297G>A		upstream_gene	N/A	NP_060587.8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR11-DT	ENST00000456120.6	TSL:5	n.21C>T		non_coding_transcript_exon	Exon 1 of 4
	WDR11-DT	ENST00000598981.5	TSL:5	n.86C>T		non_coding_transcript_exon	Exon 1 of 4
	WDR11-DT	ENST00000628194.3	TSL:2	n.240C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00893 AC: 1360 AN: 152216 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00113 AC: 390 AN: 345290 Hom.: 5 Cov.: 0 AF XY: 0.000913 AC XY: 166 AN XY: 181772

African (AFR) AF: 0.0316 AC: 314 AN: 9932

American (AMR) AF: 0.00149 AC: 22 AN: 14724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10668

East Asian (EAS) AF: 0.00 AC: 0 AN: 21744

South Asian (SAS) AF: 0.0000246 AC: 1 AN: 40702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1488

European-Non Finnish (NFE) AF: 0.0000145 AC: 3 AN: 206226

Other (OTH) AF: 0.00250 AC: 50 AN: 20010

GnomAD4 genome AF: 0.00895 AC: 1363 AN: 152334 Hom.: 18 Cov.: 33 AF XY: 0.00875 AC XY: 652 AN XY: 74502

African (AFR) AF: 0.0314 AC: 1304 AN: 41570

American (AMR) AF: 0.00235 AC: 36 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.000345 Hom.: 0

Bravo AF: 0.0102

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		-0.095
PromoterAI		-0.033	Neutral

Splicing

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

Other links and lift over

dbSNP: rs74158326; hg19: chr10-122610636;