11-117338552-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014956.5(CEP164):c.-21-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,573,528 control chromosomes in the GnomAD database, including 39,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4142 hom., cov: 31)
  • Exomes 𝑓: 0.22 (35334 hom.)
• Consequence: CEP164 NM_014956.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 11-117338552-C-T is Benign according to our data. Variant chr11-117338552-C-T is described in ClinVar as [Benign]. Clinvar id is 1245048.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-117338552-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP164	NM_014956.5	c.-21-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000278935.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP164	ENST00000278935.8	c.-21-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014956.5	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34805 AN: 151942 Hom.: 4134 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.224

GnomAD3 exomes AF: 0.224 AC: 56265 AN: 250640 Hom.: 6760 AF XY: 0.222 AC XY: 30067 AN XY: 135460

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.306

Gnomad ASJ exome AF: 0.264

Gnomad EAS exome AF: 0.137

Gnomad SAS exome AF: 0.253

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.220 AC: 312453 AN: 1421466 Hom.: 35334 Cov.: 24 AF XY: 0.220 AC XY: 156266 AN XY: 709676

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.229 AC: 34847 AN: 152062 Hom.: 4142 Cov.: 31 AF XY: 0.225 AC XY: 16754 AN XY: 74346

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.222

Alfa AF: 0.223 Hom.: 808

Bravo AF: 0.241

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	14
Dann	Benign	0.66

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: rs573801; hg19: chr11-117209268; COSMIC: COSV54041405; COSMIC: COSV54041405;