4-10098190-A-G

Variant summary

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

The NM_017491.5(WDR1):c.378-299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,908 control chromosomes in the GnomAD database, including 31,909 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 0.64 (31909 hom., cov: 33)
• Consequence: WDR1 NM_017491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.33

Genes affected

WDR1 (HGNC:12754): (WD repeat domain 1) This gene encodes a protein containing 9 WD repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, mostly including a trp-asp at the C-terminal end. WD domains are involved in protein-protein interactions. The encoded protein may help induce the disassembly of actin filaments. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR1	NM_017491.5	c.378-299T>C		intron_variant		ENST00000499869.7
WDR1	NM_005112.5	c.139-9449T>C		intron_variant
WDR1	XM_017008880.3	c.378-299T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR1	ENST00000499869.7	c.378-299T>C		intron_variant		5	NM_017491.5	P1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96774 AN: 151790 Hom.: 31890 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.638 AC: 96842 AN: 151908 Hom.: 31909 Cov.: 33 AF XY: 0.637 AC XY: 47287 AN XY: 74224

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.710

Gnomad4 OTH AF: 0.678

Alfa AF: 0.671 Hom.: 14990

Bravo AF: 0.636

Asia WGS AF: 0.594 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.019
Dann	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs2241482; hg19: chr4-10099814;