rs1043828

Positions:

• chr5-111128310-T-C
• chr5-111128310-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139281.3(WDR36):​c.*1427T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 185,036 control chromosomes in the GnomAD database, including 7,751 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 0.26 (6206 hom., cov: 31)
  • Exomes 𝑓: 0.28 (1545 hom.)
• Consequence: WDR36 NM_139281.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR36	NM_139281.3	c.*1427T>C		3_prime_UTR_variant	23/23	ENST00000513710.4	NP_644810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.*1427T>C		3_prime_UTR_variant	23/23	1	NM_139281.3	ENSP00000424628.3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39978 AN: 151800 Hom.: 6206 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.0430

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.278 AC: 9196 AN: 33118 Hom.: 1545 Cov.: 0 AF XY: 0.281 AC XY: 4289 AN XY: 15256

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.254

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.0450

Gnomad4 SAS exome AF: 0.0828

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.329

GnomAD4 genome AF: 0.263 AC: 39988 AN: 151918 Hom.: 6206 Cov.: 31 AF XY: 0.255 AC XY: 18951 AN XY: 74244

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.0429

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.286

Alfa AF: 0.333 Hom.: 17789

Bravo AF: 0.264

Asia WGS AF: 0.112 AC: 388 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1043828; hg19: chr5-110464008;