rs377552

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-169431250-A-G
• chr6-169431250-A-T

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR27	XM_011535687.4	c.2524-538T>C		intron_variant	Intron 25 of 26		XP_011533989.1
WDR27	XM_011535688.4	c.2524-538T>C		intron_variant	Intron 25 of 26		XP_011533990.1
WDR27	XR_007059231.1	n.3192-538T>C		intron_variant	Intron 25 of 27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285733	ENST00000648086.1	c.614-538T>C		intron_variant	Intron 6 of 7			ENSP00000497979.1
ENSG00000272848	ENST00000607876.2	n.232-538T>C		intron_variant	Intron 1 of 2	6
ENSG00000285733	ENST00000649579.1	n.*1082-538T>C		intron_variant	Intron 12 of 13			ENSP00000497123.1
ENSG00000285733	ENST00000650382.1	n.1054-538T>C		intron_variant	Intron 9 of 10

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 v4.3

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;