rs117083334

chr11-117381721-A-G

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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:4
• Conservation: PhyloP100: -2.32

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 194251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117381721-A-G is described in Lovd as [Benign].
• 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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP164	NM_014956.5	c.1430A>G	p.His477Arg	missense_variant	13/33	ENST00000278935.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP164	ENST00000278935.8	c.1430A>G	p.His477Arg	missense_variant	13/33	1	NM_014956.5	P1
CEP164	ENST00000533675.5	n.1685A>G		non_coding_transcript_exon_variant	9/27	2
CEP164	ENST00000533706.5	n.754A>G		non_coding_transcript_exon_variant	6/27	5

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

GnomAD3 exomes AF: 0.0241 AC: 5735 AN: 237776 Hom.: 106 AF XY: 0.0249 AC XY: 3228 AN XY: 129496

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 SAS exome AF: 0.0102

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

Gnomad4 AFR exome AF: 0.00605

Gnomad4 AMR exome AF: 0.0207

Gnomad4 ASJ exome AF: 0.0459

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.0102

Gnomad4 FIN exome AF: 0.0217

Gnomad4 NFE exome AF: 0.0384

Gnomad4 OTH exome AF: 0.0340

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

Gnomad4 AFR AF: 0.00739

Gnomad4 AMR AF: 0.0309

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00726

Gnomad4 FIN AF: 0.0184

Gnomad4 NFE AF: 0.0371

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0335 Hom.: 46

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

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 01, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Nephronophthisis 15 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	N
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs117083334; hg19: chr11-117252437; COSMIC: COSV54041331; COSMIC: COSV54041331;