11-117381775-C-G

Variant names:

• chr11-117381775-C-G
• rs59763167
• NM_014956.5:c.1484C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001440949.1(CEP164):​c.1493C>G​(p.Pro498Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,597,284 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P498T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0024 (13 hom., cov: 30)
  • Exomes 𝑓: 0.0033 (115 hom.)
• Consequence: CEP164 NM_001440949.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.95
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002693832).
• BP6: Variant 11-117381775-C-G is Benign according to our data. Variant chr11-117381775-C-G is described in ClinVar as Benign. ClinVar VariationId is 235424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0024 (365/152288) while in subpopulation SAS AF = 0.0483 (233/4822). AF 95% confidence interval is 0.0432. There are 13 homozygotes in GnomAd4. There are 242 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440949.1. 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.1484C>G	p.Pro495Arg	missense	Exon 13 of 33	NP_055771.4
	CEP164	NM_001440949.1		c.1493C>G	p.Pro498Arg	missense	Exon 13 of 33	NP_001427878.1
	CEP164	NM_001440950.1		c.1484C>G	p.Pro495Arg	missense	Exon 13 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.1484C>G	p.Pro495Arg	missense	Exon 13 of 33	ENSP00000278935.3
	CEP164	ENST00000957770.1		c.1415C>G	p.Pro472Arg	missense	Exon 10 of 30	ENSP00000627829.1
	CEP164	ENST00000939969.1		c.1406C>G	p.Pro469Arg	missense	Exon 13 of 32	ENSP00000610028.1

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 365 AN: 152170 Hom.: 13 Cov.: 30

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00688 AC: 1495 AN: 217208 AF XY: 0.00826

Gnomad AFR exome AF: 0.000240

Gnomad AMR exome AF: 0.0000621

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0171

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000137

Gnomad OTH exome AF: 0.00388

GnomAD4 exome AF: 0.00326 AC: 4708 AN: 1444996 Hom.: 115 Cov.: 35 AF XY: 0.00431 AC XY: 3093 AN XY: 717250

African (AFR) AF: 0.000483 AC: 16 AN: 33138

American (AMR) AF: 0.0000934 AC: 4 AN: 42816

Ashkenazi Jewish (ASJ) AF: 0.0000389 AC: 1 AN: 25678

East Asian (EAS) AF: 0.0173 AC: 675 AN: 38994

South Asian (SAS) AF: 0.0425 AC: 3546 AN: 83488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52012

Middle Eastern (MID) AF: 0.00106 AC: 6 AN: 5670

European-Non Finnish (NFE) AF: 0.000133 AC: 147 AN: 1103594

Other (OTH) AF: 0.00525 AC: 313 AN: 59606

GnomAD4 genome AF: 0.00240 AC: 365 AN: 152288 Hom.: 13 Cov.: 30 AF XY: 0.00325 AC XY: 242 AN XY: 74466

African (AFR) AF: 0.000457 AC: 19 AN: 41548

American (AMR) AF: 0.000131 AC: 2 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5170

South Asian (SAS) AF: 0.0483 AC: 233 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68034

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000214 Hom.: 1

Bravo AF: 0.00132

ExAC AF: 0.00679 AC: 819

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.17
DANN	Benign	0.97
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.5	L
PhyloP100		-2.0
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.15
Sift	Benign	0.051	T
Sift4G	Benign	0.61	T
Polyphen		0.90	P
Vest4		0.10
MVP		0.29
MPC		0.12
ClinPred		0.0072	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.14
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs59763167; hg19: chr11-117252491;