5-111097400-A-G

Variant names:

• chr5-111097400-A-G
• rs1993465
• NM_139281.3:c.291+221A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139281.3(WDR36):​c.291+221A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,044 control chromosomes in the GnomAD database, including 23,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (23340 hom., cov: 32)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.857
• Publications: 12 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-111097400-A-G is Benign according to our data. Variant chr5-111097400-A-G is described in ClinVar as Benign. ClinVar VariationId is 1269375.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	NM_139281.3	MANE Select	c.291+221A>G		intron	N/A	NP_644810.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	ENST00000513710.4	TSL:1 MANE Select	c.291+221A>G		intron	N/A	ENSP00000424628.3
	WDR36	ENST00000946910.1		c.295+217A>G		intron	N/A	ENSP00000616969.1
	WDR36	ENST00000856283.1		c.291+221A>G		intron	N/A	ENSP00000526342.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82466 AN: 151926 Hom.: 23301 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.543 AC: 82563 AN: 152044 Hom.: 23340 Cov.: 32 AF XY: 0.548 AC XY: 40754 AN XY: 74324

African (AFR) AF: 0.688 AC: 28523 AN: 41484

American (AMR) AF: 0.548 AC: 8373 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1708 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2064 AN: 5172

South Asian (SAS) AF: 0.687 AC: 3312 AN: 4820

European-Finnish (FIN) AF: 0.548 AC: 5779 AN: 10548

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31160 AN: 67962

Other (OTH) AF: 0.533 AC: 1125 AN: 2110

Alfa AF: 0.398 Hom.: 1182

Bravo AF: 0.542

Asia WGS AF: 0.540 AC: 1879 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.9
DANN	Benign	0.76
PhyloP100		0.86
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: rs1993465; hg19: chr5-110433098; COSMIC: COSV72411561; COSMIC: COSV72411561;