Genetic Variant WDR90:c.560-7C>T (chr16-650988-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_145294.5(WDR90):c.560-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,612,946 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 29 hom. )

Consequence

WDR90
NM_145294.5 splice_region, intron

Scores

Splicing: ADA: 0.00001472

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.49

Publications

0 publications found

Variant links:

Genes affected

WDR90 (HGNC:26960): (WD repeat domain 90) Involved in cilium assembly. Located in centriole. [provided by Alliance of Genome Resources, Apr 2022]

WDR90 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-650988-C-T is Benign according to our data. Variant chr16-650988-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2645835.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145294.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WDR90	NM_145294.5	MANE Select	c.560-7C>T	splice_region intron	N/A	NP_660337.3
WDR90	NM_001438707.1		c.560-7C>T	splice_region intron	N/A	NP_001425636.1
WDR90	NM_001438708.1		c.560-7C>T	splice_region intron	N/A	NP_001425637.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDR90	ENST00000293879.9	TSL:5 MANE Select	c.560-7C>T	splice_region intron	N/A	ENSP00000293879.4	Q96KV7-1
WDR90	ENST00000420061.6	TSL:1	n.624-7C>T	splice_region intron	N/A
WDR90	ENST00000549648.5	TSL:1	n.624-7C>T	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00432

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00375

AC:

933

AN:

248876

AF XY:

0.00420

show subpopulations

Gnomad AFR exome

AF:

0.000388

Gnomad AMR exome

AF:

0.000985

Gnomad ASJ exome

AF:

0.00259

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.000465

Gnomad NFE exome

AF:

0.00512

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.00407

AC:

5944

AN:

1460616

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

3094

AN XY:

726610

show subpopulations

African (AFR)

AF:

0.000597

AC:

AN:

33480

American (AMR)

AF:

0.00136

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00283

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39698

South Asian (SAS)

AF:

0.00919

AC:

793

AN:

86250

European-Finnish (FIN)

AF:

0.000573

AC:

AN:

52318

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00420

AC:

4671

AN:

1111870

Other (OTH)

AF:

0.00386

AC:

233

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

338

676

1015

1353

1691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00272

AC:

414

AN:

152330

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41580

American (AMR)

AF:

0.00248

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00432

AC:

294

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00356

Hom.:

Bravo

AF:

0.00266

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00594

EpiControl

AF:

0.00516

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.24

(source)

DANN

Benign

0.48

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0020

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over