chr5-77437554-C-T

Variant names:

• chr5-77437554-C-T
• rs919224
• NM_018268.4:c.1005-130G>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.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
• Publications: 8 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=-0.59).
• 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 rank	MANE	Protein	UniProt
WDR41	NM_018268.4	c.1005-130G>A		intron_variant	Intron 10 of 12	ENST00000296679.9	NP_060738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR41	ENST00000296679.9	c.1005-130G>A		intron_variant	Intron 10 of 12	1	NM_018268.4	ENSP00000296679.4

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

African (AFR) AF: 0.341 AC: 5806 AN: 17004

American (AMR) AF: 0.406 AC: 14029 AN: 34530

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 9221 AN: 18280

East Asian (EAS) AF: 0.345 AC: 12285 AN: 35610

South Asian (SAS) AF: 0.276 AC: 17334 AN: 62756

European-Finnish (FIN) AF: 0.375 AC: 14267 AN: 38042

Middle Eastern (MID) AF: 0.366 AC: 1453 AN: 3970

European-Non Finnish (NFE) AF: 0.372 AC: 146788 AN: 394754

Other (OTH) AF: 0.377 AC: 12382 AN: 32862

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

African (AFR) AF: 0.339 AC: 14070 AN: 41470

American (AMR) AF: 0.383 AC: 5848 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1728 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1828 AN: 5176

South Asian (SAS) AF: 0.281 AC: 1353 AN: 4820

European-Finnish (FIN) AF: 0.361 AC: 3809 AN: 10550

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25176 AN: 67960

Other (OTH) AF: 0.376 AC: 793 AN: 2110

Alfa AF: 0.372 Hom.: 33291

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
PhyloP100		0.23
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: rs919224; hg19: chr5-76733379;