Genetic Variant WDR45B:c.*523T>C (chr17-82615396-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019613.4(WDR45B):c.*523T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 186,110 control chromosomes in the GnomAD database, including 63,127 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 0.83 ( 52177 hom., cov: 31)

Exomes 𝑓: 0.80 ( 10950 hom. )

Consequence

WDR45B
NM_019613.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Variant links:

Genes affected

WDR45B (HGNC:25072): (WD repeat domain 45B) This gene encodes a member of the WIPI or SVP1 family of WD40 repeat-containing proteins. The protein contains seven WD40 repeats that are thought to fold into a beta-propeller structure that mediates protein-protein interactions, and a conserved motif for interaction with phospholipids. The human genome contains several pseudogenes of this gene. [provided by RefSeq, Jul 2008]

WDR45B links:

FOXK2 (HGNC:6036): (forkhead box K2) The protein encoded by this gene contains a fork head DNA binding domain. This protein can bind to the purine-rich motifs of the HIV long terminal repeat (LTR), and to the similar purine-rich motif in the interleukin 2 (IL2) promoter. It may be involved in the regulation of viral and cellular promoter elements. [provided by RefSeq, Jul 2008]

FOXK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
WDR45B	NM_019613.4 link	c.*523T>C	3_prime_UTR_variant	Exon 10 of 10	ENST00000392325.9	NP_062559.2	Q5MNZ6
WDR45B	XM_005256377.6 link	c.*523T>C	3_prime_UTR_variant	Exon 9 of 9		XP_005256434.1
WDR45B	XM_047436412.1 link	c.*523T>C	3_prime_UTR_variant	Exon 8 of 8		XP_047292368.1
WDR45B	XM_047436413.1 link	c.*523T>C	3_prime_UTR_variant	Exon 10 of 10		XP_047292369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR45B	ENST00000392325 link	c.*523T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_019613.4	ENSP00000376139.4		Q5MNZ6

Frequencies

GnomAD3 genomes

AF:

0.826

AC:

125585

AN:

152044

Hom.:

52129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.897

Gnomad AMI

AF:

0.760

Gnomad AMR

AF:

0.832

Gnomad ASJ

AF:

0.897

Gnomad EAS

AF:

0.792

Gnomad SAS

AF:

0.907

Gnomad FIN

AF:

0.771

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.784

Gnomad OTH

AF:

0.833

GnomAD4 exome

AF:

0.797

AC:

27067

AN:

33948

Hom.:

10950

Cov.:

AF XY:

0.808

AC XY:

14444

AN XY:

17880

show subpopulations

Gnomad4 AFR exome

AF:

0.894

Gnomad4 AMR exome

AF:

0.825

Gnomad4 ASJ exome

AF:

0.882

Gnomad4 EAS exome

AF:

0.783

Gnomad4 SAS exome

AF:

0.911

Gnomad4 FIN exome

AF:

0.763

Gnomad4 NFE exome

AF:

0.762

Gnomad4 OTH exome

AF:

0.794

GnomAD4 genome

AF:

0.826

AC:

125694

AN:

152162

Hom.:

52177

Cov.:

AF XY:

0.827

AC XY:

61507

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.897

Gnomad4 AMR

AF:

0.833

Gnomad4 ASJ

AF:

0.897

Gnomad4 EAS

AF:

0.792

Gnomad4 SAS

AF:

0.909

Gnomad4 FIN

AF:

0.771

Gnomad4 NFE

AF:

0.784

Gnomad4 OTH

AF:

0.834

Alfa

AF:

0.801

Hom.:

57158

Bravo

AF:

0.833

Asia WGS

AF:

0.878

AC:

3052

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.50

DANN

Benign

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over