NM_018268.4:c.167+5240T>C

Variant names:

• chr5-77484217-A-G
• rs163035
• NM_018268.4:c.167+5240T>C

Variant summary

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

The NM_018268.4(WDR41):​c.167+5240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,110 control chromosomes in the GnomAD database, including 31,495 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 0.63 (31495 hom., cov: 32)
• Consequence: WDR41 NM_018268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 8 publications found

Genes affected

WDR41 (HGNC:25601): (WD repeat domain 41) Contributes to guanyl-nucleotide exchange factor activity. Involved in regulation of autophagy. Located in cytoplasm. Part of guanyl-nucleotide exchange factor complex. Colocalizes with Atg1/ULK1 kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

LOC124901009 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR41	NM_018268.4	c.167+5240T>C		intron_variant	Intron 2 of 12	ENST00000296679.9	NP_060738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR41	ENST00000296679.9	c.167+5240T>C		intron_variant	Intron 2 of 12	1	NM_018268.4	ENSP00000296679.4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95322 AN: 151992 Hom.: 31443 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.627 AC: 95432 AN: 152110 Hom.: 31495 Cov.: 32 AF XY: 0.627 AC XY: 46604 AN XY: 74328

African (AFR) AF: 0.833 AC: 34600 AN: 41522

American (AMR) AF: 0.673 AC: 10287 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2491 AN: 3472

East Asian (EAS) AF: 0.592 AC: 3061 AN: 5168

South Asian (SAS) AF: 0.657 AC: 3169 AN: 4824

European-Finnish (FIN) AF: 0.485 AC: 5121 AN: 10554

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34637 AN: 67964

Other (OTH) AF: 0.630 AC: 1331 AN: 2114

Alfa AF: 0.553 Hom.: 39946

Bravo AF: 0.655

Asia WGS AF: 0.628 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		0.13
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: rs163035; hg19: chr5-76780042; COSMIC: COSV57000754;