rs2066987

Positions:

• chr5-77560792-T-A

Variant summary

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

The ENST00000509971.5(WDR41):​c.42+59687A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 152,254 control chromosomes in the GnomAD database, including 488 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 0.069 (488 hom., cov: 32)
• Consequence: WDR41 ENST00000509971.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.977

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR41	XM_011543505.3	c.42+59687A>T		intron_variant
WDR41	XM_047417349.1	c.-142-6215A>T		intron_variant
WDR41	XM_047417350.1	c.-68-20256A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR41	ENST00000509971.5	c.42+59687A>T		intron_variant		3
WDR41	ENST00000509858.5	n.99-20256A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10455 AN: 152136 Hom.: 485 Cov.: 32

Gnomad AFR AF: 0.0786

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0500

Gnomad FIN AF: 0.0529

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0602

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

GnomAD4 genome AF: 0.0687 AC: 10467 AN: 152254 Hom.: 488 Cov.: 32 AF XY: 0.0700 AC XY: 5213 AN XY: 74426

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0498

Gnomad4 FIN AF: 0.0529

Gnomad4 NFE AF: 0.0576

Gnomad4 OTH AF: 0.0595

Alfa AF: 0.0624 Hom.: 41

Bravo AF: 0.0748

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.5
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2066987; hg19: chr5-76856617;