chr5-77512310-T-C

Variant names:

• chr5-77512310-T-C
• rs10514104
• ENST00000509971.5:c.43-22738A>G

Variant summary

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

The ENST00000509971.5(WDR41):​c.43-22738A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 131,950 control chromosomes in the GnomAD database, including 1,285 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 0.13 (1285 hom., cov: 26)
• Consequence: WDR41 ENST00000509971.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR41	XM_011543505.3	c.43-22738A>G		intron_variant	Intron 1 of 12		XP_011541807.1
WDR41	XM_047417349.1	c.11+28148A>G		intron_variant	Intron 3 of 13		XP_047273305.1
WDR41	XM_047417350.1	c.11+28148A>G		intron_variant	Intron 2 of 12		XP_047273306.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR41	ENST00000509971.5	c.43-22738A>G		intron_variant	Intron 1 of 5	3		ENSP00000422922.1
WDR41	ENST00000509858.5	n.178-22753A>G		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 17410 AN: 131842 Hom.: 1282 Cov.: 26

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0644

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0543

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.132 AC: 17419 AN: 131950 Hom.: 1285 Cov.: 26 AF XY: 0.132 AC XY: 8448 AN XY: 64092

African (AFR) AF: 0.0389 AC: 1265 AN: 32558

American (AMR) AF: 0.121 AC: 1511 AN: 12534

Ashkenazi Jewish (ASJ) AF: 0.0644 AC: 210 AN: 3260

East Asian (EAS) AF: 0.148 AC: 724 AN: 4908

South Asian (SAS) AF: 0.184 AC: 788 AN: 4292

European-Finnish (FIN) AF: 0.181 AC: 1604 AN: 8874

Middle Eastern (MID) AF: 0.0537 AC: 13 AN: 242

European-Non Finnish (NFE) AF: 0.175 AC: 10968 AN: 62610

Other (OTH) AF: 0.125 AC: 233 AN: 1862

Alfa AF: 0.144 Hom.: 4637

Bravo AF: 0.105

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.67
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10514104; hg19: chr5-76808135;