rs8258

Variant names:

• chr11-117412960-T-C
• rs8258
• NM_014956.5:c.*792T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014956.5(CEP164):​c.*792T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,122 control chromosomes in the GnomAD database, including 27,935 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (27929 hom., cov: 32)
  • Exomes 𝑓: 0.67 (6 hom.)
• Consequence: CEP164 NM_014956.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.96
• Publications: 23 publications found

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]

CEP164 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• nephronophthisis 15

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, G2P
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	NM_014956.5	MANE Select	c.*792T>C		3_prime_UTR	Exon 33 of 33	NP_055771.4
	CEP164	NM_001440949.1		c.*792T>C		3_prime_UTR	Exon 33 of 33	NP_001427878.1
	CEP164	NM_001440950.1		c.*792T>C		3_prime_UTR	Exon 33 of 33	NP_001427879.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	ENST00000278935.8	TSL:1 MANE Select	c.*792T>C		3_prime_UTR	Exon 33 of 33	ENSP00000278935.3
	CEP164	ENST00000533706.5	TSL:5	n.4729T>C		non_coding_transcript_exon	Exon 27 of 27
	CEP164	ENST00000533433.1	TSL:2	n.*130T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91133 AN: 151974 Hom.: 27894 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.667 AC: 20 AN: 30 Hom.: 6 Cov.: 0 AF XY: 0.700 AC XY: 14 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 16 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.600 AC: 91216 AN: 152092 Hom.: 27929 Cov.: 32 AF XY: 0.594 AC XY: 44148 AN XY: 74334

African (AFR) AF: 0.647 AC: 26848 AN: 41504

American (AMR) AF: 0.430 AC: 6571 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1994 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1879 AN: 5130

South Asian (SAS) AF: 0.489 AC: 2362 AN: 4828

European-Finnish (FIN) AF: 0.612 AC: 6484 AN: 10588

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43058 AN: 67958

Other (OTH) AF: 0.604 AC: 1278 AN: 2116

Alfa AF: 0.611 Hom.: 133511

Bravo AF: 0.587

Asia WGS AF: 0.460 AC: 1598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.060
DANN	Benign	0.49
PhyloP100		-4.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8258; hg19: chr11-117283676;