chr5-77490017-A-G

Position:

• chr5-77490017-A-G

Variant summary

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

The NM_018268.4(WDR41):​c.52-445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,056 control chromosomes in the GnomAD database, including 18,553 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 0.49 (18553 hom., cov: 32)
• Consequence: WDR41 NM_018268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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]

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 (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR41	NM_018268.4	c.52-445T>C		intron_variant		ENST00000296679.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR41	ENST00000296679.9	c.52-445T>C		intron_variant		1	NM_018268.4	P1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74033 AN: 151938 Hom.: 18532 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.487 AC: 74099 AN: 152056 Hom.: 18553 Cov.: 32 AF XY: 0.487 AC XY: 36177 AN XY: 74310

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.501

Alfa AF: 0.453 Hom.: 2009

Bravo AF: 0.507

Asia WGS AF: 0.502 AC: 1746 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	5.7
DANN	Benign	0.67

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: rs163024; hg19: chr5-76785842;