ENST00000508154.1:n.76-1740T>C

Variant names:

• chr5-77428774-A-G
• rs335636
• ENST00000508154.1:n.76-1740T>C

Variant summary

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

The ENST00000508154.1(WDR41):​n.76-1740T>C variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR41	ENST00000508154.1	n.76-1740T>C		intron_variant	Intron 1 of 1	3
WDR41	ENST00000512033.1	n.415-1740T>C		intron_variant	Intron 2 of 2	5
WDR41	ENST00000514878.1	n.64-1740T>C		intron_variant	Intron 1 of 2	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.844 AC: 34962 AN: 41444

American (AMR) AF: 0.674 AC: 10294 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2488 AN: 3472

East Asian (EAS) AF: 0.595 AC: 3077 AN: 5170

South Asian (SAS) AF: 0.657 AC: 3167 AN: 4824

European-Finnish (FIN) AF: 0.484 AC: 5115 AN: 10572

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34643 AN: 67948

Other (OTH) AF: 0.633 AC: 1332 AN: 2104

Alfa AF: 0.554 Hom.: 39912

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
PhyloP100		-0.55
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: rs335636; hg19: chr5-76724599;