rs9271

Positions:

• chr17-82615396-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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]

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR45B	NM_019613.4	c.*523T>C		3_prime_UTR_variant	10/10	ENST00000392325.9
WDR45B	XM_005256377.6	c.*523T>C		3_prime_UTR_variant	9/9
WDR45B	XM_047436412.1	c.*523T>C		3_prime_UTR_variant	8/8
WDR45B	XM_047436413.1	c.*523T>C		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR45B	ENST00000392325.9	c.*523T>C		3_prime_UTR_variant	10/10	1	NM_019613.4	P1
WDR45B	ENST00000572583.5	c.*897T>C		3_prime_UTR_variant, NMD_transcript_variant	10/10	1
WDR45B	ENST00000576517.1	c.*201+322T>C		intron_variant, NMD_transcript_variant		3
FOXK2	ENST00000574694.1	n.39+11721A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125585 AN: 152044 Hom.: 52129 Cov.: 31

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.: 0 AF XY: 0.808 AC XY: 14444 AN XY: 17880

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.: 31 AF XY: 0.827 AC XY: 61507 AN XY: 74370

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

Other links and lift over

dbSNP: rs9271; hg19: chr17-80573272; COSMIC: COSV66408649; COSMIC: COSV66408649;