rs116483743

chr5-111098650-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_139281.3(WDR36):c.292-72T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,011,370 control chromosomes in the GnomAD database, including 10 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 0.0054 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (6 hom.)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0054 (822/152302) while in subpopulation AFR AF= 0.0188 (781/41568). AF 95% confidence interval is 0.0177. There are 4 homozygotes in gnomad4. There are 416 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR36	NM_139281.3	c.292-72T>G		intron_variant		ENST00000513710.4
WDR36	XM_047416729.1	c.292-72T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR36	ENST00000513710.4	c.292-72T>G		intron_variant		1	NM_139281.3	P1
WDR36	ENST00000504122.2	n.174-72T>G		intron_variant, non_coding_transcript_variant		4
WDR36	ENST00000505303.5	n.428-72T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00538 AC: 818 AN: 152184 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

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: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000583 AC: 501 AN: 859068 Hom.: 6 AF XY: 0.000478 AC XY: 216 AN XY: 452148

Gnomad4 AFR exome AF: 0.0178

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000411

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000283

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.00540 AC: 822 AN: 152302 Hom.: 4 Cov.: 32 AF XY: 0.00559 AC XY: 416 AN XY: 74458

Gnomad4 AFR AF: 0.0188

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00684 Hom.: 0

Bravo AF: 0.00620

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.60
Dann	Benign	0.65

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: rs116483743; hg19: chr5-110434348;