rs897837

Positions:

• chr11-117390772-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014956.5(CEP164):​c.1935-5C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,613,500 control chromosomes in the GnomAD database, including 22,936 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1525 hom., cov: 31)
  • Exomes 𝑓: 0.17 (21411 hom.)
• Consequence: CEP164 NM_014956.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0005488
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.655

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 (BayesDel_noAF=-0.83).
• BP6: Variant 11-117390772-C-G is Benign according to our data. Variant chr11-117390772-C-G is described in ClinVar as [Benign]. Clinvar id is 260476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117390772-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP164	NM_014956.5	c.1935-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000278935.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP164	ENST00000278935.8	c.1935-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014956.5	P1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19367 AN: 151866 Hom.: 1524 Cov.: 31

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.0973

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.134

GnomAD3 exomes AF: 0.169 AC: 42588 AN: 251290 Hom.: 4115 AF XY: 0.170 AC XY: 23095 AN XY: 135810

Gnomad AFR exome AF: 0.0294

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.124

Gnomad SAS exome AF: 0.196

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.167 AC: 243902 AN: 1461516 Hom.: 21411 Cov.: 33 AF XY: 0.168 AC XY: 122187 AN XY: 727086

Gnomad4 AFR exome AF: 0.0292

Gnomad4 AMR exome AF: 0.255

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.127 AC: 19371 AN: 151984 Hom.: 1525 Cov.: 31 AF XY: 0.129 AC XY: 9555 AN XY: 74266

Gnomad4 AFR AF: 0.0331

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.133

Alfa AF: 0.156 Hom.: 660

Bravo AF: 0.130

Asia WGS AF: 0.130 AC: 450 AN: 3478

EpiCase AF: 0.162

EpiControl AF: 0.157

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Nephronophthisis 15 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00055
dbscSNV1_RF	Benign	0.070
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: rs897837; hg19: chr11-117261488; COSMIC: COSV54038326;