chr5-111107529-C-T

Variant names:

• chr5-111107529-C-T
• rs10043631
• NM_139281.3:c.1326+90C>T

Variant summary

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

The NM_139281.3(WDR36):​c.1326+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,517,830 control chromosomes in the GnomAD database, including 180,361 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 0.54 (22693 hom., cov: 32)
  • Exomes 𝑓: 0.47 (157668 hom.)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 10 publications found

Genes affected

WDR36 (HGNC:30696): (WD repeat domain 36) 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. Mutations in this gene have been associated with adult-onset primary open-angle glaucoma (POAG). [provided by RefSeq, Jul 2008]

WDR36 Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, G

  Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139281.3. 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
	WDR36	NM_139281.3	MANE Select	c.1326+90C>T		intron	N/A	NP_644810.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	ENST00000513710.4	TSL:1 MANE Select	c.1326+90C>T		intron	N/A	ENSP00000424628.3
	WDR36	ENST00000505303.5	TSL:5	n.1462+90C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81212 AN: 150958 Hom.: 22662 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.474 AC: 647377 AN: 1366754 Hom.: 157668 AF XY: 0.479 AC XY: 325749 AN XY: 679524

African (AFR) AF: 0.677 AC: 20835 AN: 30778

American (AMR) AF: 0.623 AC: 23316 AN: 37438

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12210 AN: 24652

East Asian (EAS) AF: 0.361 AC: 13680 AN: 37932

South Asian (SAS) AF: 0.678 AC: 53263 AN: 78564

European-Finnish (FIN) AF: 0.528 AC: 24079 AN: 45624

Middle Eastern (MID) AF: 0.605 AC: 2559 AN: 4232

European-Non Finnish (NFE) AF: 0.447 AC: 469781 AN: 1050828

Other (OTH) AF: 0.488 AC: 27654 AN: 56706

GnomAD4 genome AF: 0.538 AC: 81299 AN: 151076 Hom.: 22693 Cov.: 32 AF XY: 0.544 AC XY: 40160 AN XY: 73838

African (AFR) AF: 0.672 AC: 27757 AN: 41332

American (AMR) AF: 0.546 AC: 8263 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1695 AN: 3446

East Asian (EAS) AF: 0.395 AC: 2032 AN: 5150

South Asian (SAS) AF: 0.680 AC: 3280 AN: 4820

European-Finnish (FIN) AF: 0.549 AC: 5794 AN: 10552

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 30855 AN: 67350

Other (OTH) AF: 0.527 AC: 1104 AN: 2096

Alfa AF: 0.519 Hom.: 2810

Bravo AF: 0.536

Asia WGS AF: 0.530 AC: 1845 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.25
PhyloP100		-0.18
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: rs10043631; hg19: chr5-110443228;