rs3734905

Positions:

• chr6-169558886-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182552.5(WDR27):​c.2645+13533C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 152,254 control chromosomes in the GnomAD database, including 893 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 0.091 (893 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDR27 NM_182552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR27	NM_182552.5	c.2645+13533C>T		intron_variant		ENST00000448612.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR27	ENST00000448612.6	c.2645+13533C>T		intron_variant		1	NM_182552.5	A2

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13855 AN: 152136 Hom.: 892 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0719

Gnomad OTH AF: 0.102

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0911 AC: 13872 AN: 152254 Hom.: 893 Cov.: 32 AF XY: 0.0965 AC XY: 7182 AN XY: 74442

Gnomad4 AFR AF: 0.0643

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0719

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0819 Hom.: 1259

Bravo AF: 0.0933

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3734905; hg19: chr6-169958982;