6-169431250-A-G

Variant names:

• chr6-169431250-A-G
• rs377552
• ENST00000648086.1:c.614-538T>C

Variant summary

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

The ENST00000648086.1(ENSG00000285733):​c.614-538T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,068 control chromosomes in the GnomAD database, including 17,767 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 0.46 (17767 hom., cov: 32)
• Consequence: ENSG00000285733 ENST00000648086.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 7 publications found

Genes affected

ENSG00000285733 (HGNC:):

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648086.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285733	ENST00000648086.1		c.614-538T>C		intron	N/A	ENSP00000497979.1
	ENSG00000272848	ENST00000607876.2	TSL:6	n.232-538T>C		intron	N/A
	ENSG00000285733	ENST00000649579.1		n.*1082-538T>C		intron	N/A	ENSP00000497123.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69978 AN: 151950 Hom.: 17763 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.0535

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.460 AC: 69987 AN: 152068 Hom.: 17767 Cov.: 32 AF XY: 0.452 AC XY: 33618 AN XY: 74346

African (AFR) AF: 0.331 AC: 13729 AN: 41464

American (AMR) AF: 0.365 AC: 5574 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1827 AN: 3468

East Asian (EAS) AF: 0.0529 AC: 274 AN: 5182

South Asian (SAS) AF: 0.298 AC: 1437 AN: 4826

European-Finnish (FIN) AF: 0.580 AC: 6121 AN: 10562

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39364 AN: 67968

Other (OTH) AF: 0.464 AC: 980 AN: 2112

Alfa AF: 0.531 Hom.: 35982

Bravo AF: 0.440

Asia WGS AF: 0.188 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.53
PhyloP100		-0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs377552; hg19: chr6-169831345; COSMIC: COSV74169393;