rs693147

chr11-117396038-A-C

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.3090-16A>C 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 0.597 in 1,613,544 control chromosomes in the GnomAD database, including 292,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27686 hom., cov: 32)
  • Exomes 𝑓: 0.60 (264476 hom.)
• Consequence: CEP164 NM_014956.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.03

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=-0.91).
• BP6: Variant 11-117396038-A-C is Benign according to our data. Variant chr11-117396038-A-C is described in ClinVar as [Benign]. Clinvar id is 260483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP164	NM_014956.5	c.3090-16A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000278935.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP164	ENST00000278935.8	c.3090-16A>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014956.5	P1
CEP164	ENST00000533223.1	n.3972-16A>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
CEP164	ENST00000533675.5	n.3317-16A>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2
CEP164	ENST00000533706.5	n.2414-16A>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90669 AN: 151832 Hom.: 27648 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.602

GnomAD3 exomes AF: 0.539 AC: 135269 AN: 251188 Hom.: 38754 AF XY: 0.545 AC XY: 73991 AN XY: 135746

Gnomad AFR exome AF: 0.651

Gnomad AMR exome AF: 0.292

Gnomad ASJ exome AF: 0.554

Gnomad EAS exome AF: 0.345

Gnomad SAS exome AF: 0.493

Gnomad FIN exome AF: 0.599

Gnomad NFE exome AF: 0.628

Gnomad OTH exome AF: 0.544

GnomAD4 exome AF: 0.597 AC: 872013 AN: 1461594 Hom.: 264476 Cov.: 55 AF XY: 0.595 AC XY: 432436 AN XY: 727114

Gnomad4 AFR exome AF: 0.651

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.388

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.594

Gnomad4 NFE exome AF: 0.624

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.597 AC: 90754 AN: 151950 Hom.: 27686 Cov.: 32 AF XY: 0.590 AC XY: 43830 AN XY: 74278

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.604

Alfa AF: 0.620 Hom.: 24373

Bravo AF: 0.587

Asia WGS AF: 0.458 AC: 1593 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	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
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

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.50
Dann	Benign	0.42

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: rs693147; hg19: chr11-117266754; COSMIC: COSV54042087; COSMIC: COSV54042087;