11-117412084-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014956.5(CEP164):c.4299G>T(p.Ser1433=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.96 in 1,614,096 control chromosomes in the GnomAD database, including 744,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S1433S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.95 (69441 hom., cov: 32)
  • Exomes 𝑓: 0.96 (674898 hom.)
• Consequence: CEP164 NM_014956.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.18

Genes affected

CEP164 (HGNC:29182): (centrosomal protein 164) This gene encodes a centrosomal protein involved in microtubule organization, DNA damage response, and chromosome segregation. The encoded protein is required for assembly of primary cilia and localizes to mature centrioles. Defects in this gene are a cause of nephronophthisis-related ciliopathies. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-117412084-G-T is Benign according to our data. Variant chr11-117412084-G-T is described in ClinVar as [Benign]. Clinvar id is 260490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117412084-G-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP164	NM_014956.5	c.4299G>T	p.Ser1433=	synonymous_variant	33/33	ENST00000278935.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP164	ENST00000278935.8	c.4299G>T	p.Ser1433=	synonymous_variant	33/33	1	NM_014956.5	P1

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145170 AN: 152156 Hom.: 69383 Cov.: 32

Gnomad AFR AF: 0.960

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.981

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.951

GnomAD3 exomes AF: 0.936 AC: 235225 AN: 251424 Hom.: 110384 AF XY: 0.936 AC XY: 127123 AN XY: 135882

Gnomad AFR exome AF: 0.961

Gnomad AMR exome AF: 0.889

Gnomad ASJ exome AF: 0.929

Gnomad EAS exome AF: 0.839

Gnomad SAS exome AF: 0.874

Gnomad FIN exome AF: 0.979

Gnomad NFE exome AF: 0.970

Gnomad OTH exome AF: 0.947

GnomAD4 exome AF: 0.960 AC: 1403704 AN: 1461822 Hom.: 674898 Cov.: 53 AF XY: 0.958 AC XY: 696691 AN XY: 727222

Gnomad4 AFR exome AF: 0.958

Gnomad4 AMR exome AF: 0.892

Gnomad4 ASJ exome AF: 0.931

Gnomad4 EAS exome AF: 0.867

Gnomad4 SAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.980

Gnomad4 NFE exome AF: 0.973

Gnomad4 OTH exome AF: 0.951

GnomAD4 genome AF: 0.954 AC: 145286 AN: 152274 Hom.: 69441 Cov.: 32 AF XY: 0.951 AC XY: 70823 AN XY: 74438

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.913

Gnomad4 ASJ AF: 0.936

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.981

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.951

Alfa AF: 0.964 Hom.: 87018

Bravo AF: 0.951

Asia WGS AF: 0.865 AC: 3007 AN: 3478

EpiCase AF: 0.967

EpiControl AF: 0.966

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Nephronophthisis 15 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.60
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs522885; hg19: chr11-117282800;