rs75908454

chr6-169570527-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR27	NM_182552.5	c.2645+1892A>G		intron_variant		ENST00000448612.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR27	ENST00000448612.6	c.2645+1892A>G		intron_variant		1	NM_182552.5	A2

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

Gnomad4 AFR AF: 0.0891

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0487

Gnomad4 FIN AF: 0.0353

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0399 Hom.: 25

Bravo AF: 0.0459

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.8
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs75908454; hg19: chr6-169970623;