11-117412084-G-T

Variant names:

• chr11-117412084-G-T
• rs522885
• NM_014956.5:c.4299G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014956.5(CEP164):​c.4299G>T​(p.Ser1433Ser) 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:6
• Conservation: PhyloP100: -1.18
• Publications: 18 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 11-117412084-G-T is Benign according to our data. Variant chr11-117412084-G-T is described in ClinVar as Benign. ClinVar VariationId is 260490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.4299G>T	p.Ser1433Ser	synonymous	Exon 33 of 33	NP_055771.4
	CEP164	NM_001440949.1		c.4305G>T	p.Ser1435Ser	synonymous	Exon 33 of 33	NP_001427878.1
	CEP164	NM_001440950.1		c.4299G>T	p.Ser1433Ser	synonymous	Exon 33 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.4299G>T	p.Ser1433Ser	synonymous	Exon 33 of 33	ENSP00000278935.3
	CEP164	ENST00000528706.5	TSL:2	n.1152G>T		non_coding_transcript_exon	Exon 4 of 4
	CEP164	ENST00000533433.1	TSL:2	n.819G>T		non_coding_transcript_exon	Exon 2 of 2

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

GnomAD2 exomes AF: 0.936 AC: 235225 AN: 251424 AF XY: 0.936

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 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

African (AFR) AF: 0.958 AC: 32065 AN: 33478

American (AMR) AF: 0.892 AC: 39872 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 24338 AN: 26134

East Asian (EAS) AF: 0.867 AC: 34419 AN: 39700

South Asian (SAS) AF: 0.875 AC: 75463 AN: 86246

European-Finnish (FIN) AF: 0.980 AC: 52333 AN: 53416

Middle Eastern (MID) AF: 0.934 AC: 5388 AN: 5768

European-Non Finnish (NFE) AF: 0.973 AC: 1082371 AN: 1111972

Other (OTH) AF: 0.951 AC: 57455 AN: 60392

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

African (AFR) AF: 0.960 AC: 39902 AN: 41548

American (AMR) AF: 0.913 AC: 13969 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3245 AN: 3468

East Asian (EAS) AF: 0.840 AC: 4326 AN: 5148

South Asian (SAS) AF: 0.858 AC: 4142 AN: 4828

European-Finnish (FIN) AF: 0.981 AC: 10420 AN: 10624

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.971 AC: 66084 AN: 68036

Other (OTH) AF: 0.951 AC: 2012 AN: 2116

Alfa AF: 0.963 Hom.: 122057

Bravo AF: 0.951

Asia WGS AF: 0.865 AC: 3007 AN: 3478

EpiCase AF: 0.967

EpiControl AF: 0.966

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Nephronophthisis 15 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.60
DANN	Benign	0.41
PhyloP100		-1.2
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: rs522885; hg19: chr11-117282800; COSMIC: COSV107229647; COSMIC: COSV107229647;