11-117391137-C-T

Variant names:

• chr11-117391137-C-T
• rs494553
• NM_014956.5:c.2205C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_014956.5(CEP164):​c.2205C>T​(p.Ser735Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,613,770 control chromosomes in the GnomAD database, including 2,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (188 hom., cov: 31)
  • Exomes 𝑓: 0.049 (1927 hom.)
• Consequence: CEP164 NM_014956.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0610
• Publications: 6 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):

• CEP164-related ciliopathy

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

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 11-117391137-C-T is Benign according to our data. Variant chr11-117391137-C-T is described in ClinVar as Benign. ClinVar VariationId is 260478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0569 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	NM_014956.5	MANE Select	c.2205C>T	p.Ser735Ser	synonymous	Exon 17 of 33	NP_055771.4
	CEP164	NM_001440949.1		c.2214C>T	p.Ser738Ser	synonymous	Exon 17 of 33	NP_001427878.1
	CEP164	NM_001440950.1		c.2205C>T	p.Ser735Ser	synonymous	Exon 17 of 33	NP_001427879.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	ENST00000278935.8	TSL:1 MANE Select	c.2205C>T	p.Ser735Ser	synonymous	Exon 17 of 33	ENSP00000278935.3	Q9UPV0-1
	CEP164	ENST00000533223.1	TSL:1	n.3087C>T		non_coding_transcript_exon	Exon 3 of 16
	CEP164	ENST00000957770.1		c.2136C>T	p.Ser712Ser	synonymous	Exon 14 of 30	ENSP00000627829.1

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5720 AN: 151982 Hom.: 188 Cov.: 31

Gnomad AFR AF: 0.00822

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.0681

Gnomad EAS AF: 0.000778

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0584

Gnomad OTH AF: 0.0445

GnomAD2 exomes AF: 0.0385 AC: 9677 AN: 251048 AF XY: 0.0397

Gnomad AFR exome AF: 0.00733

Gnomad AMR exome AF: 0.0230

Gnomad ASJ exome AF: 0.0682

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.0351

Gnomad NFE exome AF: 0.0580

Gnomad OTH exome AF: 0.0397

GnomAD4 exome AF: 0.0489 AC: 71505 AN: 1461668 Hom.: 1927 Cov.: 33 AF XY: 0.0484 AC XY: 35196 AN XY: 727130

African (AFR) AF: 0.00729 AC: 244 AN: 33466

American (AMR) AF: 0.0232 AC: 1038 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 1724 AN: 26132

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0170 AC: 1469 AN: 86252

European-Finnish (FIN) AF: 0.0353 AC: 1886 AN: 53416

Middle Eastern (MID) AF: 0.0399 AC: 226 AN: 5662

European-Non Finnish (NFE) AF: 0.0558 AC: 62090 AN: 1111946

Other (OTH) AF: 0.0468 AC: 2823 AN: 60374

GnomAD4 genome AF: 0.0376 AC: 5717 AN: 152102 Hom.: 188 Cov.: 31 AF XY: 0.0361 AC XY: 2681 AN XY: 74338

African (AFR) AF: 0.00819 AC: 340 AN: 41510

American (AMR) AF: 0.0275 AC: 421 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 236 AN: 3466

East Asian (EAS) AF: 0.000779 AC: 4 AN: 5132

South Asian (SAS) AF: 0.0139 AC: 67 AN: 4818

European-Finnish (FIN) AF: 0.0392 AC: 415 AN: 10582

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0584 AC: 3972 AN: 67996

Other (OTH) AF: 0.0441 AC: 93 AN: 2110

Alfa AF: 0.0463 Hom.: 147

Bravo AF: 0.0363

Asia WGS AF: 0.00808 AC: 29 AN: 3478

EpiCase AF: 0.0611

EpiControl AF: 0.0622

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.1
DANN	Benign	0.38
PhyloP100		-0.061
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs494553; hg19: chr11-117261853; COSMIC: COSV54041345; COSMIC: COSV54041345;