rs140306974

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The ENST00000306467.10(CEP120):c.2647C>T(p.Arg883Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,613,560 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R883H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00059 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

CEP120
ENST00000306467.10 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 7.16

Publications

1 publications found

Variant links:

Genes affected

CEP120 (HGNC:26690): (centrosomal protein 120) This gene encodes a protein that functions in the microtubule-dependent coupling of the nucleus and the centrosome. A similar protein in mouse plays a role in both interkinetic nuclear migration, which is a characteristic pattern of nuclear movement in neural progenitors, and in neural progenitor self-renewal. Mutations in this gene are predicted to result in neurogenic defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

CEP120 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
Joubert syndrome 31
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
short-rib thoracic dysplasia 13 with or without polydactyly
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Jeune syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with ocular defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP120 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03636524).

BP6

Variant 5-123350023-G-A is Benign according to our data. Variant chr5-123350023-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 542763.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000591 (90/152160) while in subpopulation AFR AF = 0.0019 (79/41528). AF 95% confidence interval is 0.00156. There are 1 homozygotes in GnomAd4. There are 47 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000306467.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP120	NM_001375405.1	MANE Select	c.2647C>T	p.Arg883Cys	missense	Exon 19 of 20	NP_001362334.1
CEP120	NM_153223.4		c.2647C>T	p.Arg883Cys	missense	Exon 20 of 21	NP_694955.2
CEP120	NM_001166226.2		c.2569C>T	p.Arg857Cys	missense	Exon 19 of 20	NP_001159698.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP120	ENST00000306467.10	TSL:5 MANE Select	c.2647C>T	p.Arg883Cys	missense	Exon 19 of 20	ENSP00000303058.6
CEP120	ENST00000508138.5	TSL:1	n.*2219C>T		non_coding_transcript_exon	Exon 22 of 23	ENSP00000422234.1
CEP120	ENST00000513565.6	TSL:1	n.*2051C>T		non_coding_transcript_exon	Exon 20 of 21	ENSP00000422089.2

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000156

AC:

AN:

250762

AF XY:

0.0000959

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000739

AC:

108

AN:

1461400

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

726960

show subpopulations

African (AFR)

AF:

0.00224

AC:

AN:

33466

American (AMR)

AF:

0.0000672

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39610

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1111762

Other (OTH)

AF:

0.000248

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000591

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41528

American (AMR)

AF:

0.000458

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

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:

0.000289

Hom.:

Bravo

AF:

0.000892

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000181

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

CEP120-related disorder (1)

Inborn genetic diseases (1)

not provided (1)

Short-rib thoracic dysplasia 13 with or without polydactyly (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.025

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

7.2

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.17

Sift

Uncertain

0.025

Sift4G

Uncertain

0.046

Polyphen

0.33

Vest4

0.55

MVP

0.26

MPC

0.46

ClinPred

0.11

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.25

Mutation Taster

=75/25

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over