chr6-169699302-C-T

Variant names:

• chr6-169699302-C-T
• rs4073926
• NM_182552.5:c.-8+2249G>A

Variant summary

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

The NM_182552.5(WDR27):​c.-8+2249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,878 control chromosomes in the GnomAD database, including 14,088 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 0.40 (14088 hom., cov: 32)
• Consequence: WDR27 NM_182552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 14 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR27	NM_182552.5	c.-8+2249G>A		intron_variant	Intron 1 of 25	ENST00000448612.6	NP_872358.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR27	ENST00000448612.6	c.-8+2249G>A		intron_variant	Intron 1 of 25	1	NM_182552.5	ENSP00000416289.1
ENSG00000285733	ENST00000648086.1	c.-8+2249G>A		intron_variant	Intron 1 of 7			ENSP00000497979.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60306 AN: 151760 Hom.: 14037 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.398 AC: 60417 AN: 151878 Hom.: 14088 Cov.: 32 AF XY: 0.405 AC XY: 30051 AN XY: 74220

African (AFR) AF: 0.524 AC: 21691 AN: 41402

American (AMR) AF: 0.523 AC: 7982 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3468

East Asian (EAS) AF: 0.938 AC: 4802 AN: 5122

South Asian (SAS) AF: 0.462 AC: 2227 AN: 4822

European-Finnish (FIN) AF: 0.284 AC: 2996 AN: 10546

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.272 AC: 18497 AN: 67940

Other (OTH) AF: 0.395 AC: 833 AN: 2108

Alfa AF: 0.323 Hom.: 33303

Bravo AF: 0.424

Asia WGS AF: 0.696 AC: 2417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.30
PhyloP100		-0.015
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: rs4073926; hg19: chr6-170099398;