17-82615396-A-G

Variant names:

• chr17-82615396-A-G
• rs9271
• ENST00000572583.5:n.*897T>C

Variant summary

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

The ENST00000572583.5(WDR45B):​n.*897T>C variant causes a non coding transcript exon 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 ENST00000572583.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000572583.5. 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
	WDR45B	NM_019613.4	MANE Select	c.*523T>C		3_prime_UTR	Exon 10 of 10	NP_062559.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR45B	ENST00000572583.5	TSL:1	n.*897T>C		non_coding_transcript_exon	Exon 10 of 10	ENSP00000461488.1
	WDR45B	ENST00000392325.9	TSL:1 MANE Select	c.*523T>C		3_prime_UTR	Exon 10 of 10	ENSP00000376139.4
	WDR45B	ENST00000572583.5	TSL:1	n.*897T>C		3_prime_UTR	Exon 10 of 10	ENSP00000461488.1

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

African (AFR) AF: 0.894 AC: 805 AN: 900

American (AMR) AF: 0.825 AC: 2859 AN: 3466

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 471 AN: 534

East Asian (EAS) AF: 0.783 AC: 2015 AN: 2574

South Asian (SAS) AF: 0.911 AC: 4212 AN: 4624

European-Finnish (FIN) AF: 0.763 AC: 778 AN: 1020

Middle Eastern (MID) AF: 0.778 AC: 70 AN: 90

European-Non Finnish (NFE) AF: 0.762 AC: 14651 AN: 19222

Other (OTH) AF: 0.794 AC: 1206 AN: 1518

GnomAD4 genome AF: 0.826 AC: 125694 AN: 152162 Hom.: 52177 Cov.: 31 AF XY: 0.827 AC XY: 61507 AN XY: 74370

African (AFR) AF: 0.897 AC: 37229 AN: 41516

American (AMR) AF: 0.833 AC: 12730 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3114 AN: 3472

East Asian (EAS) AF: 0.792 AC: 4093 AN: 5170

South Asian (SAS) AF: 0.909 AC: 4376 AN: 4816

European-Finnish (FIN) AF: 0.771 AC: 8153 AN: 10580

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53288 AN: 68000

Other (OTH) AF: 0.834 AC: 1764 AN: 2116

Alfa AF: 0.804 Hom.: 155841

Bravo AF: 0.833

Asia WGS AF: 0.878 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.50
DANN	Benign	0.42
PhyloP100		-1.0
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: rs9271; hg19: chr17-80573272; COSMIC: COSV66408649; COSMIC: COSV66408649;