rs75908454

Variant names:

• chr6-169570527-T-C
• rs75908454
• NM_182552.5:c.2645+1892A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182552.5(WDR27):​c.2645+1892A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 152,312 control chromosomes in the GnomAD database, including 261 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 0.046 (261 hom., cov: 33)
• Consequence: WDR27 NM_182552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 6 publications found

Genes affected

WDR27 (HGNC:21248): (WD repeat domain 27) This gene encodes a protein with multiple WD repeats. Proteins with these repeats may form scaffolds for protein-protein interaction and play key roles in cell signalling. Alternative splicing results in multiple transcript variants, but the full-length structure of some of these variants cannot be determined. [provided by RefSeq, Nov 2015]

ENSG00000285733 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182552.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR27	NM_182552.5	MANE Select	c.2645+1892A>G		intron	N/A	NP_872358.4
	WDR27	NM_001202550.2		c.2142+12309A>G		intron	N/A	NP_001189479.1
	WDR27	NM_001350623.2		c.1950+12309A>G		intron	N/A	NP_001337552.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR27	ENST00000448612.6	TSL:1 MANE Select	c.2645+1892A>G		intron	N/A	ENSP00000416289.1
	WDR27	ENST00000423258.5	TSL:1	c.2142+12309A>G		intron	N/A	ENSP00000397869.1
	ENSG00000285733	ENST00000648086.1		c.533+12309A>G		intron	N/A	ENSP00000497979.1

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 7006 AN: 152194 Hom.: 259 Cov.: 33

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0420

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

GnomAD4 genome AF: 0.0461 AC: 7028 AN: 152312 Hom.: 261 Cov.: 33 AF XY: 0.0475 AC XY: 3540 AN XY: 74466

African (AFR) AF: 0.0891 AC: 3705 AN: 41562

American (AMR) AF: 0.0214 AC: 327 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3472

East Asian (EAS) AF: 0.114 AC: 589 AN: 5176

South Asian (SAS) AF: 0.0487 AC: 235 AN: 4826

European-Finnish (FIN) AF: 0.0353 AC: 375 AN: 10626

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1490 AN: 68022

Other (OTH) AF: 0.0449 AC: 95 AN: 2116

Alfa AF: 0.0419 Hom.: 28

Bravo AF: 0.0459

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.8
DANN	Benign	0.72
PhyloP100		0.0010
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: rs75908454; hg19: chr6-169970623;