5-77447656-A-T

Variant names:

• chr5-77447656-A-T
• rs163016
• NM_018268.4:c.697+2104T>A

Variant summary

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

The NM_018268.4(WDR41):​c.697+2104T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,976 control chromosomes in the GnomAD database, including 19,828 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 0.51 (19828 hom., cov: 32)
• Consequence: WDR41 NM_018268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR41	NM_018268.4	c.697+2104T>A		intron_variant	Intron 8 of 12	ENST00000296679.9	NP_060738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR41	ENST00000296679.9	c.697+2104T>A		intron_variant	Intron 8 of 12	1	NM_018268.4	ENSP00000296679.4

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76734 AN: 151858 Hom.: 19805 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.505 AC: 76800 AN: 151976 Hom.: 19828 Cov.: 32 AF XY: 0.505 AC XY: 37486 AN XY: 74286

African (AFR) AF: 0.592 AC: 24551 AN: 41438

American (AMR) AF: 0.579 AC: 8833 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2182 AN: 3470

East Asian (EAS) AF: 0.481 AC: 2479 AN: 5158

South Asian (SAS) AF: 0.498 AC: 2402 AN: 4824

European-Finnish (FIN) AF: 0.443 AC: 4677 AN: 10564

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29951 AN: 67946

Other (OTH) AF: 0.525 AC: 1108 AN: 2112

Alfa AF: 0.470 Hom.: 2158

Bravo AF: 0.526

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.35
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: rs163016; hg19: chr5-76743481;