5-111093543-C-T

Variant names:

• chr5-111093543-C-T
• rs1971050
• NM_139281.3:c.162+925C>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.162+925C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,254 control chromosomes in the GnomAD database, including 60,218 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 0.89 (60218 hom., cov: 32)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.162+925C>T		intron_variant	Intron 1 of 22	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.162+925C>T		intron_variant	Intron 1 of 20		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.162+925C>T		intron_variant	Intron 1 of 22	1	NM_139281.3	ENSP00000424628.3
WDR36	ENST00000505303.5	n.298+925C>T		intron_variant	Intron 1 of 14	5
WDR36	ENST00000515784.1	n.272+925C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134818 AN: 152136 Hom.: 60157 Cov.: 32

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.888

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

GnomAD4 genome AF: 0.886 AC: 134938 AN: 152254 Hom.: 60218 Cov.: 32 AF XY: 0.884 AC XY: 65822 AN XY: 74442

African (AFR) AF: 0.971 AC: 40365 AN: 41562

American (AMR) AF: 0.901 AC: 13780 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3045 AN: 3470

East Asian (EAS) AF: 0.617 AC: 3188 AN: 5168

South Asian (SAS) AF: 0.916 AC: 4423 AN: 4828

European-Finnish (FIN) AF: 0.867 AC: 9185 AN: 10598

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.852 AC: 57953 AN: 68004

Other (OTH) AF: 0.888 AC: 1879 AN: 2116

Alfa AF: 0.864 Hom.: 17701

Bravo AF: 0.890

Asia WGS AF: 0.802 AC: 2791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.39
PhyloP100		-0.37
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: rs1971050; hg19: chr5-110429241; COSMIC: COSV72411484; COSMIC: COSV72411484;