5-111118108-T-C

Variant names:

• chr5-111118108-T-C
• rs10491424
• NM_139281.3:c.1797-905T>C

Variant summary

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

The NM_139281.3(WDR36):​c.1797-905T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,010 control chromosomes in the GnomAD database, including 12,497 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 0.40 (12497 hom., cov: 32)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.451 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.1797-905T>C		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.1797-905T>C		intron	N/A	ENSP00000424628.3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60744 AN: 151892 Hom.: 12479 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.409

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.400 AC: 60800 AN: 152010 Hom.: 12497 Cov.: 32 AF XY: 0.405 AC XY: 30090 AN XY: 74296

African (AFR) AF: 0.446 AC: 18484 AN: 41466

American (AMR) AF: 0.460 AC: 7018 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1407 AN: 3464

East Asian (EAS) AF: 0.329 AC: 1704 AN: 5174

South Asian (SAS) AF: 0.446 AC: 2150 AN: 4822

European-Finnish (FIN) AF: 0.437 AC: 4615 AN: 10556

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24118 AN: 67948

Other (OTH) AF: 0.405 AC: 857 AN: 2114

Alfa AF: 0.237 Hom.: 553

Bravo AF: 0.404

Asia WGS AF: 0.377 AC: 1313 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.65
PhyloP100		-1.3
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: rs10491424; hg19: chr5-110453806;