NM_014956.5:c.4119C>T

Variant names:

• chr11-117410850-C-T
• rs73016324
• NM_014956.5:c.4119C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014956.5(CEP164):​c.4119C>T​(p.Asn1373Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 1,612,948 control chromosomes in the GnomAD database, including 1,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (84 hom., cov: 32)
  • Exomes 𝑓: 0.034 (983 hom.)
• Consequence: CEP164 NM_014956.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.294
• Publications: 5 publications found

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]

CEP164 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• nephronophthisis 15

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, G2P
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-117410850-C-T is Benign according to our data. Variant chr11-117410850-C-T is described in ClinVar as Benign. ClinVar VariationId is 260489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.294 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0259 (3937/152266) while in subpopulation NFE AF = 0.0389 (2647/68004). AF 95% confidence interval is 0.0377. There are 84 homozygotes in GnomAd4. There are 1957 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 84 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	NM_014956.5	MANE Select	c.4119C>T	p.Asn1373Asn	synonymous	Exon 31 of 33	NP_055771.4
	CEP164	NM_001440949.1		c.4125C>T	p.Asn1375Asn	synonymous	Exon 31 of 33	NP_001427878.1
	CEP164	NM_001440950.1		c.4119C>T	p.Asn1373Asn	synonymous	Exon 31 of 33	NP_001427879.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	ENST00000278935.8	TSL:1 MANE Select	c.4119C>T	p.Asn1373Asn	synonymous	Exon 31 of 33	ENSP00000278935.3
	CEP164	ENST00000528706.5	TSL:2	n.972C>T		non_coding_transcript_exon	Exon 2 of 4
	CEP164	ENST00000532187.1	TSL:3	n.177C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3935 AN: 152148 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.00589

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0210

GnomAD2 exomes AF: 0.0288 AC: 7176 AN: 249230 AF XY: 0.0299

Gnomad AFR exome AF: 0.00708

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0321

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.0499

Gnomad NFE exome AF: 0.0375

Gnomad OTH exome AF: 0.0292

GnomAD4 exome AF: 0.0343 AC: 50087 AN: 1460682 Hom.: 983 Cov.: 30 AF XY: 0.0345 AC XY: 25036 AN XY: 726462

African (AFR) AF: 0.00502 AC: 168 AN: 33472

American (AMR) AF: 0.0114 AC: 510 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.0332 AC: 866 AN: 26106

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39686

South Asian (SAS) AF: 0.0296 AC: 2543 AN: 85928

European-Finnish (FIN) AF: 0.0486 AC: 2592 AN: 53338

Middle Eastern (MID) AF: 0.0161 AC: 93 AN: 5764

European-Non Finnish (NFE) AF: 0.0374 AC: 41565 AN: 1111382

Other (OTH) AF: 0.0289 AC: 1745 AN: 60338

GnomAD4 genome AF: 0.0259 AC: 3937 AN: 152266 Hom.: 84 Cov.: 32 AF XY: 0.0263 AC XY: 1957 AN XY: 74448

African (AFR) AF: 0.00587 AC: 244 AN: 41566

American (AMR) AF: 0.0132 AC: 202 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4822

European-Finnish (FIN) AF: 0.0522 AC: 554 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0389 AC: 2647 AN: 68004

Other (OTH) AF: 0.0213 AC: 45 AN: 2114

Alfa AF: 0.0350 Hom.: 177

Bravo AF: 0.0222

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.0352

EpiControl AF: 0.0354

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nephronophthisis 15 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.40
DANN	Benign	0.46
PhyloP100		-0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73016324; hg19: chr11-117281566;