rs151170797

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The ENST00000257287.5(CEP135):ā€‹c.2755A>Cā€‹(p.Arg919=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00197 in 1,584,730 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0019 ( 2 hom., cov: 32)
Exomes š‘“: 0.0020 ( 5 hom. )

Consequence

CEP135
ENST00000257287.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.59
Variant links:
Genes affected
CEP135 (HGNC:29086): (centrosomal protein 135) This gene encodes a centrosomal protein, which acts as a scaffolding protein during early centriole biogenesis, and is also required for centriole-centriole cohesion during interphase. Mutations in this gene are associated with autosomal recessive primary microcephaly-8. [provided by RefSeq, Jun 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 4-56011938-A-C is Benign according to our data. Variant chr4-56011938-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 128698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-56011938-A-C is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00194 (296/152370) while in subpopulation NFE AF= 0.00244 (166/68042). AF 95% confidence interval is 0.00214. There are 2 homozygotes in gnomad4. There are 157 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CEP135NM_025009.5 linkuse as main transcriptc.2755A>C p.Arg919= synonymous_variant 21/26 ENST00000257287.5 NP_079285.2
CEP135XM_006714055.4 linkuse as main transcriptc.2722A>C p.Arg908= synonymous_variant 21/26 XP_006714118.1
CEP135XM_005265788.5 linkuse as main transcriptc.1684A>C p.Arg562= synonymous_variant 14/19 XP_005265845.1
CEP135XM_011534412.2 linkuse as main transcriptc.1225A>C p.Arg409= synonymous_variant 11/16 XP_011532714.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CEP135ENST00000257287.5 linkuse as main transcriptc.2755A>C p.Arg919= synonymous_variant 21/261 NM_025009.5 ENSP00000257287 P1Q66GS9-1
CEP135ENST00000506202.1 linkuse as main transcriptn.2705A>C non_coding_transcript_exon_variant 14/191
CEP135ENST00000706801.1 linkuse as main transcriptn.820A>C non_coding_transcript_exon_variant 5/10

Frequencies

GnomAD3 genomes
AF:
0.00194
AC:
296
AN:
152252
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.0143
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00772
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00244
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00186
AC:
419
AN:
225278
Hom.:
2
AF XY:
0.00188
AC XY:
230
AN XY:
122348
show subpopulations
Gnomad AFR exome
AF:
0.000338
Gnomad AMR exome
AF:
0.00140
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000309
Gnomad FIN exome
AF:
0.00654
Gnomad NFE exome
AF:
0.00208
Gnomad OTH exome
AF:
0.00170
GnomAD4 exome
AF:
0.00197
AC:
2827
AN:
1432360
Hom.:
5
Cov.:
31
AF XY:
0.00197
AC XY:
1400
AN XY:
712140
show subpopulations
Gnomad4 AFR exome
AF:
0.000157
Gnomad4 AMR exome
AF:
0.00133
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000297
Gnomad4 FIN exome
AF:
0.00568
Gnomad4 NFE exome
AF:
0.00216
Gnomad4 OTH exome
AF:
0.00117
GnomAD4 genome
AF:
0.00194
AC:
296
AN:
152370
Hom.:
2
Cov.:
32
AF XY:
0.00211
AC XY:
157
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00772
Gnomad4 NFE
AF:
0.00244
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00154
Hom.:
0
Bravo
AF:
0.00136
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingGeneDxNov 30, 2018- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 30, 2023- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2024CEP135: BP4, BS2 -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoSep 27, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
11
DANN
Benign
0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs151170797; hg19: chr4-56878104; API