rs117473319

chr11-117394931-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_014956.5(CEP164):c.2772C>G(p.Leu924=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,614,106 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (14 hom.)
• Consequence: CEP164 NM_014956.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.642

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 11-117394931-C-G is Benign according to our data. Variant chr11-117394931-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 260480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117394931-C-G is described in Lovd as [Benign]. Variant chr11-117394931-C-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.642 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00196 (298/152318) while in subpopulation NFE AF= 0.00368 (250/68022). AF 95% confidence interval is 0.0033. There are 0 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP164	NM_014956.5	c.2772C>G	p.Leu924=	synonymous_variant	22/33	ENST00000278935.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP164	ENST00000278935.8	c.2772C>G	p.Leu924=	synonymous_variant	22/33	1	NM_014956.5	P1
CEP164	ENST00000533223.1	n.3654C>G		non_coding_transcript_exon_variant	8/16	1
CEP164	ENST00000533675.5	n.2880C>G		non_coding_transcript_exon_variant	17/27	2
CEP164	ENST00000533706.5	n.2096C>G		non_coding_transcript_exon_variant	15/27	5

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 300 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000915

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00369

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00174 AC: 438 AN: 251476 Hom.: 2 AF XY: 0.00169 AC XY: 230 AN XY: 135912

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00319

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00328 AC: 4795 AN: 1461788 Hom.: 14 Cov.: 32 AF XY: 0.00311 AC XY: 2258 AN XY: 727212

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.000650

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.00405

Gnomad4 OTH exome AF: 0.00272

GnomAD4 genome AF: 0.00196 AC: 298 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.00140 AC XY: 104 AN XY: 74482

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00368

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00298 Hom.: 0

Bravo AF: 0.00200

EpiCase AF: 0.00256

EpiControl AF: 0.00237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Nephronophthisis 15 Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 08, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Jun 28, 2017	- -

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	2.9
Dann	Benign	0.62

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: rs117473319; hg19: chr11-117265647;