rs200103555

Variant names:

• chr11-117396185-GCTGGGGGCTGGGGC-G
• rs200103555
• NM_014956.5:c.3216+20_3216+33delCTGGGGGCTGGGGC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_014956.5(CEP164):​c.3216+20_3216+33delCTGGGGGCTGGGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 1,610,816 control chromosomes in the GnomAD database, including 668 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (37 hom., cov: 28)
  • Exomes 𝑓: 0.021 (631 hom.)
• Consequence: CEP164 NM_014956.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.24
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 11-117396185-GCTGGGGGCTGGGGC-G is Benign according to our data. Variant chr11-117396185-GCTGGGGGCTGGGGC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 473083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0165 (2506/152054) while in subpopulation NFE AF = 0.0253 (1721/67968). AF 95% confidence interval is 0.0243. There are 37 homozygotes in GnomAd4. There are 1183 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 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.3216+20_3216+33delCTGGGGGCTGGGGC		intron	N/A	NP_055771.4
	CEP164	NM_001440949.1		c.3222+20_3222+33delCTGGGGGCTGGGGC		intron	N/A	NP_001427878.1
	CEP164	NM_001440950.1		c.3216+20_3216+33delCTGGGGGCTGGGGC		intron	N/A	NP_001427879.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	ENST00000278935.8	TSL:1 MANE Select	c.3216+6_3216+19delCTGGGGGCTGGGGC		splice_region intron	N/A	ENSP00000278935.3
	CEP164	ENST00000533223.1	TSL:1	n.4098+6_4098+19delCTGGGGGCTGGGGC		splice_region intron	N/A
	CEP164	ENST00000533675.5	TSL:2	n.3443+6_3443+19delCTGGGGGCTGGGGC		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2508 AN: 151940 Hom.: 37 Cov.: 28

Gnomad AFR AF: 0.00435

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0159

GnomAD2 exomes AF: 0.0175 AC: 4316 AN: 247082 AF XY: 0.0172

Gnomad AFR exome AF: 0.00354

Gnomad AMR exome AF: 0.0175

Gnomad ASJ exome AF: 0.0199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0226

Gnomad NFE exome AF: 0.0250

Gnomad OTH exome AF: 0.0226

GnomAD4 exome AF: 0.0208 AC: 30292 AN: 1458762 Hom.: 631 AF XY: 0.0205 AC XY: 14890 AN XY: 725750

African (AFR) AF: 0.00332 AC: 111 AN: 33440

American (AMR) AF: 0.0173 AC: 775 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0211 AC: 551 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00237 AC: 204 AN: 86156

European-Finnish (FIN) AF: 0.0236 AC: 1257 AN: 53250

Middle Eastern (MID) AF: 0.00385 AC: 22 AN: 5718

European-Non Finnish (NFE) AF: 0.0236 AC: 26178 AN: 1109386

Other (OTH) AF: 0.0198 AC: 1194 AN: 60304

GnomAD4 genome AF: 0.0165 AC: 2506 AN: 152054 Hom.: 37 Cov.: 28 AF XY: 0.0159 AC XY: 1183 AN XY: 74318

African (AFR) AF: 0.00434 AC: 180 AN: 41488

American (AMR) AF: 0.0179 AC: 273 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4814

European-Finnish (FIN) AF: 0.0219 AC: 232 AN: 10580

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0253 AC: 1721 AN: 67968

Other (OTH) AF: 0.0157 AC: 33 AN: 2102

Alfa AF: 0.0215 Hom.: 14

Bravo AF: 0.0159

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0250

EpiControl AF: 0.0251

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs200103555; hg19: chr11-117266901;