rs151170797

Variant names:

• chr4-56011938-A-C
• rs151170797
• NM_025009.5:c.2755A>C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_025009.5(CEP135):​c.2755A>C​(p.Arg919Arg) 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (5 hom.)
• Consequence: CEP135 NM_025009.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 6.59

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]

ACMG classification

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 rank	MANE	Protein	UniProt
CEP135	NM_025009.5	c.2755A>C	p.Arg919Arg	synonymous_variant	Exon 21 of 26	ENST00000257287.5	NP_079285.2
CEP135	XM_006714055.4	c.2722A>C	p.Arg908Arg	synonymous_variant	Exon 21 of 26		XP_006714118.1
CEP135	XM_005265788.5	c.1684A>C	p.Arg562Arg	synonymous_variant	Exon 14 of 19		XP_005265845.1
CEP135	XM_011534412.2	c.1225A>C	p.Arg409Arg	synonymous_variant	Exon 11 of 16		XP_011532714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP135	ENST00000257287.5	c.2755A>C	p.Arg919Arg	synonymous_variant	Exon 21 of 26	1	NM_025009.5	ENSP00000257287.3
CEP135	ENST00000506202.1	n.2705A>C		non_coding_transcript_exon_variant	Exon 14 of 19	1
CEP135	ENST00000706801.1	n.820A>C		non_coding_transcript_exon_variant	Exon 5 of 10

Frequencies

GnomAD3 genomes AF: 0.00194 AC: 296 AN: 152252 Hom.: 2 Cov.: 32

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

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

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

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

Submissions by phenotype

not provided Benign:3

Nov 30, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CEP135: BP4, BS2 -

not specified Benign:1

Sep 27, 2013

Genetic Services Laboratory, University of Chicago

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	-0.46
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

Other links and lift over

dbSNP: rs151170797; hg19: chr4-56878104;