chr5-123346272-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001375405.1(CEP120):​c.*247T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 383,468 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 8 hom., cov: 33)
Exomes 𝑓: 0.00074 ( 1 hom. )

Consequence

CEP120
NM_001375405.1 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.555

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 5-123346272-A-T is Benign according to our data. Variant chr5-123346272-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1213615.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00614 (935/152326) while in subpopulation AFR AF = 0.0209 (871/41576). AF 95% confidence interval is 0.0198. There are 8 homozygotes in GnomAd4. There are 443 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEP120NM_001375405.1 linkc.*247T>A 3_prime_UTR_variant Exon 20 of 20 ENST00000306467.10 NP_001362334.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEP120ENST00000306467.10 linkc.*247T>A 3_prime_UTR_variant Exon 20 of 20 5 NM_001375405.1 ENSP00000303058.6 Q8N960-1

Frequencies

GnomAD3 genomes
AF:
0.00613
AC:
933
AN:
152208
Hom.:
7
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0210
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00347
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:
0.0000147
Gnomad OTH
AF:
0.00479
GnomAD4 exome
AF:
0.000735
AC:
170
AN:
231142
Hom.:
1
Cov.:
0
AF XY:
0.000609
AC XY:
73
AN XY:
119918
show subpopulations
African (AFR)
AF:
0.0187
AC:
120
AN:
6412
American (AMR)
AF:
0.00192
AC:
16
AN:
8334
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
8164
East Asian (EAS)
AF:
0.00
AC:
0
AN:
17458
South Asian (SAS)
AF:
0.00
AC:
0
AN:
13398
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
14434
Middle Eastern (MID)
AF:
0.000864
AC:
1
AN:
1158
European-Non Finnish (NFE)
AF:
0.0000340
AC:
5
AN:
147260
Other (OTH)
AF:
0.00193
AC:
28
AN:
14524
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
9
19
28
38
47
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00614
AC:
935
AN:
152326
Hom.:
8
Cov.:
33
AF XY:
0.00595
AC XY:
443
AN XY:
74476
show subpopulations
African (AFR)
AF:
0.0209
AC:
871
AN:
41576
American (AMR)
AF:
0.00346
AC:
53
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68022
Other (OTH)
AF:
0.00474
AC:
10
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
45
89
134
178
223
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.00451
Hom.:
0
Bravo
AF:
0.00680
Asia WGS
AF:
0.00290
AC:
10
AN:
3468

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Oct 05, 2018
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
9.0
DANN
Benign
0.83
PhyloP100
0.56
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs112271669; hg19: chr5-122681966; API