rs143154578

Variant names:

• chr5-111119250-A-G
• rs143154578
• NM_139281.3:c.1904+130A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_139281.3(WDR36):​c.1904+130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 605,072 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High AC in GnomAdExome4 at 8 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.1904+130A>G		intron_variant	Intron 17 of 22	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.1904+130A>G		intron_variant	Intron 17 of 20		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.1904+130A>G		intron_variant	Intron 17 of 22	1	NM_139281.3	ENSP00000424628.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000132 AC: 8 AN: 605072 Hom.: 0 AF XY: 0.0000153 AC XY: 5 AN XY: 327202

African (AFR) AF: 0.00 AC: 0 AN: 17062

American (AMR) AF: 0.0000547 AC: 2 AN: 36560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20058

East Asian (EAS) AF: 0.00 AC: 0 AN: 34104

South Asian (SAS) AF: 0.00 AC: 0 AN: 65550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3906

European-Non Finnish (NFE) AF: 0.0000170 AC: 6 AN: 353074

Other (OTH) AF: 0.00 AC: 0 AN: 31880

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.64
PhyloP100		0.048
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs143154578; hg19: chr5-110454948;