rs919224

chr5-77437554-C-T

Variant summary

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

The NM_018268.4(WDR41):c.1005-130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 789,822 control chromosomes in the GnomAD database, including 53,705 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 0.36 (10079 hom., cov: 32)
  • Exomes 𝑓: 0.37 (43626 hom.)
• Consequence: WDR41 NM_018268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

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=-0.59).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR41	NM_018268.4	c.1005-130G>A		intron_variant		ENST00000296679.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR41	ENST00000296679.9	c.1005-130G>A		intron_variant		1	NM_018268.4	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55091 AN: 151896 Hom.: 10071 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.366 AC: 233565 AN: 637808 Hom.: 43626 AF XY: 0.362 AC XY: 123384 AN XY: 340920

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.345

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.377

GnomAD4 genome AF: 0.363 AC: 55125 AN: 152014 Hom.: 10079 Cov.: 32 AF XY: 0.359 AC XY: 26712 AN XY: 74304

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.376

Alfa AF: 0.374 Hom.: 22091

Bravo AF: 0.371

Asia WGS AF: 0.328 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	14
Dann	Benign	0.87

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: rs919224; hg19: chr5-76733379;