4-10098190-A-G

Variant names:

• chr4-10098190-A-G
• rs2241482
• NM_017491.5:c.378-299T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017491.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR1	NM_017491.5	MANE Select	c.378-299T>C		intron	N/A	NP_059830.1	O75083-1
	WDR1	NM_005112.5		c.139-9449T>C		intron	N/A	NP_005103.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR1	ENST00000499869.7	TSL:5 MANE Select	c.378-299T>C		intron	N/A	ENSP00000427687.1	O75083-1
	WDR1	ENST00000699794.1		c.378-299T>C		intron	N/A	ENSP00000514596.1	A0A8V8TP22
	WDR1	ENST00000867002.1		c.378-299T>C		intron	N/A	ENSP00000537061.1

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

African (AFR) AF: 0.461 AC: 19126 AN: 41466

American (AMR) AF: 0.721 AC: 11006 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2830 AN: 3466

East Asian (EAS) AF: 0.650 AC: 3345 AN: 5144

South Asian (SAS) AF: 0.557 AC: 2684 AN: 4822

European-Finnish (FIN) AF: 0.682 AC: 7183 AN: 10530

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.710 AC: 48218 AN: 67900

Other (OTH) AF: 0.678 AC: 1431 AN: 2110

Alfa AF: 0.671 Hom.: 17963

Bravo AF: 0.636

Asia WGS AF: 0.594 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.019
DANN	Benign	0.27
PhyloP100		-4.3
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: rs2241482; hg19: chr4-10099814;