4-10108981-T-C

Variant names:

• chr4-10108981-T-C
• rs4697922
• NM_017491.5:c.139-4995A>G

Variant summary

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

The NM_017491.5(WDR1):​c.139-4995A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,188 control chromosomes in the GnomAD database, including 33,590 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 0.66 (33590 hom., cov: 35)
• Consequence: WDR1 NM_017491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR1	NM_017491.5	c.139-4995A>G		intron_variant	Intron 2 of 14	ENST00000499869.7	NP_059830.1
WDR1	NM_005112.5	c.138+7132A>G		intron_variant	Intron 2 of 11		NP_005103.2
WDR1	XM_017008880.3	c.139-4995A>G		intron_variant	Intron 2 of 14		XP_016864369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR1	ENST00000499869.7	c.139-4995A>G		intron_variant	Intron 2 of 14	5	NM_017491.5	ENSP00000427687.1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99883 AN: 152070 Hom.: 33564 Cov.: 35

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.657 AC: 99962 AN: 152188 Hom.: 33590 Cov.: 35 AF XY: 0.657 AC XY: 48873 AN XY: 74418

African (AFR) AF: 0.509 AC: 21135 AN: 41492

American (AMR) AF: 0.733 AC: 11215 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2876 AN: 3468

East Asian (EAS) AF: 0.653 AC: 3384 AN: 5180

South Asian (SAS) AF: 0.561 AC: 2713 AN: 4832

European-Finnish (FIN) AF: 0.693 AC: 7334 AN: 10580

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48807 AN: 68014

Other (OTH) AF: 0.697 AC: 1473 AN: 2114

Alfa AF: 0.684 Hom.: 18365

Bravo AF: 0.656

Asia WGS AF: 0.598 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		-0.27
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: rs4697922; hg19: chr4-10110605;