rs4984906

Variant names:

• chr16-659001-C-A
• rs4984906
• NM_145294.5:c.3001C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-659001-C-A
• chr16-659001-C-G
• chr16-659001-C-T

Variant summary

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

The NM_145294.5(WDR90):​c.3001C>A​(p.Pro1001Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,612,822 control chromosomes in the GnomAD database, including 169,311 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (26232 hom., cov: 33)
  • Exomes 𝑓: 0.42 (143079 hom.)
• Consequence: WDR90 NM_145294.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604
• Publications: 38 publications found

Genes affected

WDR90 (HGNC:26960): (WD repeat domain 90) Involved in cilium assembly. Located in centriole. [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 (MetaRNN=1.2617623E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR90	NM_145294.5	c.3001C>A	p.Pro1001Thr	missense_variant	Exon 24 of 41	ENST00000293879.9	NP_660337.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR90	ENST00000293879.9	c.3001C>A	p.Pro1001Thr	missense_variant	Exon 24 of 41	5	NM_145294.5	ENSP00000293879.4

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83028 AN: 151918 Hom.: 26176 Cov.: 33

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.477

GnomAD2 exomes AF: 0.523 AC: 130041 AN: 248430 AF XY: 0.506

Gnomad AFR exome AF: 0.839

Gnomad AMR exome AF: 0.707

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.984

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.369

Gnomad OTH exome AF: 0.445

GnomAD4 exome AF: 0.419 AC: 611854 AN: 1460786 Hom.: 143079 Cov.: 56 AF XY: 0.420 AC XY: 305391 AN XY: 726680

African (AFR) AF: 0.843 AC: 28207 AN: 33480

American (AMR) AF: 0.690 AC: 30869 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 8720 AN: 26130

East Asian (EAS) AF: 0.970 AC: 38502 AN: 39700

South Asian (SAS) AF: 0.557 AC: 48046 AN: 86256

European-Finnish (FIN) AF: 0.493 AC: 25847 AN: 52470

Middle Eastern (MID) AF: 0.362 AC: 2085 AN: 5766

European-Non Finnish (NFE) AF: 0.362 AC: 402813 AN: 1111902

Other (OTH) AF: 0.443 AC: 26765 AN: 60374

GnomAD4 genome AF: 0.547 AC: 83150 AN: 152036 Hom.: 26232 Cov.: 33 AF XY: 0.555 AC XY: 41213 AN XY: 74314

African (AFR) AF: 0.820 AC: 33997 AN: 41476

American (AMR) AF: 0.584 AC: 8931 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3472

East Asian (EAS) AF: 0.977 AC: 5049 AN: 5168

South Asian (SAS) AF: 0.551 AC: 2656 AN: 4824

European-Finnish (FIN) AF: 0.486 AC: 5142 AN: 10572

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24791 AN: 67922

Other (OTH) AF: 0.482 AC: 1015 AN: 2104

Alfa AF: 0.420 Hom.: 34860

Bravo AF: 0.566

TwinsUK AF: 0.364 AC: 1348

ALSPAC AF: 0.353 AC: 1360

ESP6500AA AF: 0.806 AC: 3390

ESP6500EA AF: 0.367 AC: 3087

ExAC AF: 0.521 AC: 62946

Asia WGS AF: 0.764 AC: 2654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.057
DANN	Benign	0.24
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.12	T;T
MetaRNN	Benign	0.0000013	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.48	.;N
PhyloP100		-0.60
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.023
Sift	Benign	1.0	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;B
Vest4		0.017
MPC		0.13
ClinPred		0.024	T
GERP RS		-9.6
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.11
Mutation Taster		=98/2	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: rs4984906; hg19: chr16-709001; COSMIC: COSV53473442; COSMIC: COSV53473442;