rs335636

chr5-77428774-A-Gchr5-77428774-A-T

Variant summary

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

The ENST00000508154.1(WDR41):n.76-1740T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,020 control chromosomes in the GnomAD database, including 31,836 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 (31836 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: WDR41 ENST00000508154.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR41	ENST00000508154.1	n.76-1740T>C		intron_variant, non_coding_transcript_variant		3
WDR41	ENST00000512033.1	n.415-1740T>C		intron_variant, non_coding_transcript_variant		5
WDR41	ENST00000514878.1	n.64-1740T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95698 AN: 151902 Hom.: 31780 Cov.: 31

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.634

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.630 AC: 95812 AN: 152020 Hom.: 31836 Cov.: 31 AF XY: 0.630 AC XY: 46799 AN XY: 74292

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.633

Alfa AF: 0.541 Hom.: 29607

Bravo AF: 0.659

Asia WGS AF: 0.629 AC: 2188 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.38
Dann	Benign	0.40

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: rs335636; hg19: chr5-76724599;