rs61995733

Positions:

• chr11-117408996-C-T

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.3716C>T​(p.Pro1239Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,614,018 control chromosomes in the GnomAD database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1239P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.016 (64 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (163 hom.)
• Consequence: CEP164 NM_014956.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.19

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=0.0029952228).
• BP6: Variant 11-117408996-C-T is Benign according to our data. Variant chr11-117408996-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117408996-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0156 (2379/152202) while in subpopulation AFR AF= 0.0472 (1959/41528). AF 95% confidence interval is 0.0454. There are 64 homozygotes in gnomad4. There are 1166 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP164	NM_014956.5	c.3716C>T	p.Pro1239Leu	missense_variant	29/33	ENST00000278935.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP164	ENST00000278935.8	c.3716C>T	p.Pro1239Leu	missense_variant	29/33	1	NM_014956.5	P1

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2370 AN: 152084 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00986 AC: 2479 AN: 251376 Hom.: 66 AF XY: 0.0102 AC XY: 1386 AN XY: 135876

Gnomad AFR exome AF: 0.0470

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0193

Gnomad SAS exome AF: 0.0398

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00452 AC: 6608 AN: 1461816 Hom.: 163 Cov.: 31 AF XY: 0.00529 AC XY: 3845 AN XY: 727214

Gnomad4 AFR exome AF: 0.0514

Gnomad4 AMR exome AF: 0.00271

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0178

Gnomad4 SAS exome AF: 0.0381

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.000218

Gnomad4 OTH exome AF: 0.00823

GnomAD4 genome AF: 0.0156 AC: 2379 AN: 152202 Hom.: 64 Cov.: 32 AF XY: 0.0157 AC XY: 1166 AN XY: 74418

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.0416

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00344 Hom.: 15

Bravo AF: 0.0167

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0404 AC: 178

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0112 AC: 1356

Asia WGS AF: 0.0460 AC: 159 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Nephronophthisis 15 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.36
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00043	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.1	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.049
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.056
MPC		0.10
ClinPred		0.0059	T
GERP RS		-0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.046

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61995733; hg19: chr11-117279712; COSMIC: COSV54041739; COSMIC: COSV54041739;