chr11-117381721-A-G

Variant names:

• chr11-117381721-A-G
• rs117083334
• NM_014956.5:c.1430A>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_014956.5(CEP164):​c.1430A>G​(p.His477Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 1,609,834 control chromosomes in the GnomAD database, including 1,055 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 (★★). Synonymous variant affecting the same amino acid position (i.e. H477H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.025 (53 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1002 hom.)
• Consequence: CEP164 NM_014956.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.32
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025341213).
• BP6: Variant 11-117381721-A-G is Benign according to our data. Variant chr11-117381721-A-G is described in ClinVar as Benign. ClinVar VariationId is 194251.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 = 0.025 (3804/152240) while in subpopulation NFE AF = 0.0371 (2526/68008). AF 95% confidence interval is 0.0359. There are 53 homozygotes in GnomAd4. There are 1752 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	NM_014956.5	MANE Select	c.1430A>G	p.His477Arg	missense	Exon 13 of 33	NP_055771.4
	CEP164	NM_001440949.1		c.1439A>G	p.His480Arg	missense	Exon 13 of 33	NP_001427878.1
	CEP164	NM_001440950.1		c.1430A>G	p.His477Arg	missense	Exon 13 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.1430A>G	p.His477Arg	missense	Exon 13 of 33	ENSP00000278935.3	Q9UPV0-1
	CEP164	ENST00000957770.1		c.1361A>G	p.His454Arg	missense	Exon 10 of 30	ENSP00000627829.1
	CEP164	ENST00000939969.1		c.1352A>G	p.His451Arg	missense	Exon 13 of 32	ENSP00000610028.1

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3805 AN: 152122 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00741

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0371

Gnomad OTH AF: 0.0378

GnomAD2 exomes AF: 0.0241 AC: 5735 AN: 237776 AF XY: 0.0249

Gnomad AFR exome AF: 0.00612

Gnomad AMR exome AF: 0.0190

Gnomad ASJ exome AF: 0.0495

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.0199

Gnomad NFE exome AF: 0.0344

Gnomad OTH exome AF: 0.0288

GnomAD4 exome AF: 0.0339 AC: 49368 AN: 1457594 Hom.: 1002 Cov.: 30 AF XY: 0.0335 AC XY: 24248 AN XY: 724724

African (AFR) AF: 0.00605 AC: 202 AN: 33378

American (AMR) AF: 0.0207 AC: 917 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.0459 AC: 1192 AN: 25984

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39626

South Asian (SAS) AF: 0.0102 AC: 865 AN: 85212

European-Finnish (FIN) AF: 0.0217 AC: 1152 AN: 52966

Middle Eastern (MID) AF: 0.0547 AC: 305 AN: 5578

European-Non Finnish (NFE) AF: 0.0384 AC: 42688 AN: 1110332

Other (OTH) AF: 0.0340 AC: 2045 AN: 60150

GnomAD4 genome AF: 0.0250 AC: 3804 AN: 152240 Hom.: 53 Cov.: 32 AF XY: 0.0235 AC XY: 1752 AN XY: 74438

African (AFR) AF: 0.00739 AC: 307 AN: 41542

American (AMR) AF: 0.0309 AC: 473 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00726 AC: 35 AN: 4824

European-Finnish (FIN) AF: 0.0184 AC: 195 AN: 10618

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0371 AC: 2526 AN: 68008

Other (OTH) AF: 0.0369 AC: 78 AN: 2112

Alfa AF: 0.0323 Hom.: 164

Bravo AF: 0.0252

TwinsUK AF: 0.0396 AC: 147

ALSPAC AF: 0.0384 AC: 148

ESP6500AA AF: 0.00659 AC: 29

ESP6500EA AF: 0.0337 AC: 289

ExAC AF: 0.0225 AC: 2727

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.0020
DANN	Benign	0.26
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-2.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.020
Sift	Benign	0.54	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.020
MPC		0.13
ClinPred		0.00020	T
GERP RS		-7.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.078
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs117083334; hg19: chr11-117252437; COSMIC: COSV54041331; COSMIC: COSV54041331;