rs897836

Variant names:

• chr11-117381773-T-C
• rs897836
• NM_014956.5:c.1482T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-117381773-T-C
• chr11-117381773-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014956.5(CEP164):​c.1482T>C​(p.Pro494Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 1,600,984 control chromosomes in the GnomAD database, including 690,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (65745 hom., cov: 32)
  • Exomes 𝑓: 0.93 (624842 hom.)
• Consequence: CEP164 NM_014956.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.912
• Publications: 16 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):

• CEP164-related ciliopathy

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

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-117381773-T-C is Benign according to our data. Variant chr11-117381773-T-C is described in ClinVar as Benign. ClinVar VariationId is 260475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.912 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	NM_014956.5	MANE Select	c.1482T>C	p.Pro494Pro	synonymous	Exon 13 of 33	NP_055771.4
	CEP164	NM_001440949.1		c.1491T>C	p.Pro497Pro	synonymous	Exon 13 of 33	NP_001427878.1
	CEP164	NM_001440950.1		c.1482T>C	p.Pro494Pro	synonymous	Exon 13 of 33	NP_001427879.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	ENST00000278935.8	TSL:1 MANE Select	c.1482T>C	p.Pro494Pro	synonymous	Exon 13 of 33	ENSP00000278935.3	Q9UPV0-1
	CEP164	ENST00000957770.1		c.1413T>C	p.Pro471Pro	synonymous	Exon 10 of 30	ENSP00000627829.1
	CEP164	ENST00000939969.1		c.1404T>C	p.Pro468Pro	synonymous	Exon 13 of 32	ENSP00000610028.1

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141215 AN: 152126 Hom.: 65683 Cov.: 32

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.915

GnomAD2 exomes AF: 0.908 AC: 203366 AN: 223894 AF XY: 0.907

Gnomad AFR exome AF: 0.956

Gnomad AMR exome AF: 0.871

Gnomad ASJ exome AF: 0.882

Gnomad EAS exome AF: 0.846

Gnomad FIN exome AF: 0.952

Gnomad NFE exome AF: 0.931

Gnomad OTH exome AF: 0.915

GnomAD4 exome AF: 0.928 AC: 1344930 AN: 1448740 Hom.: 624842 Cov.: 60 AF XY: 0.926 AC XY: 666561 AN XY: 719464

African (AFR) AF: 0.953 AC: 31658 AN: 33204

American (AMR) AF: 0.874 AC: 37809 AN: 43250

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 22818 AN: 25738

East Asian (EAS) AF: 0.869 AC: 34048 AN: 39180

South Asian (SAS) AF: 0.865 AC: 72584 AN: 83864

European-Finnish (FIN) AF: 0.954 AC: 49850 AN: 52280

Middle Eastern (MID) AF: 0.905 AC: 5111 AN: 5646

European-Non Finnish (NFE) AF: 0.937 AC: 1035932 AN: 1105782

Other (OTH) AF: 0.922 AC: 55120 AN: 59796

GnomAD4 genome AF: 0.928 AC: 141335 AN: 152244 Hom.: 65745 Cov.: 32 AF XY: 0.927 AC XY: 68992 AN XY: 74440

African (AFR) AF: 0.956 AC: 39732 AN: 41544

American (AMR) AF: 0.892 AC: 13635 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3075 AN: 3470

East Asian (EAS) AF: 0.847 AC: 4374 AN: 5162

South Asian (SAS) AF: 0.854 AC: 4113 AN: 4816

European-Finnish (FIN) AF: 0.950 AC: 10086 AN: 10614

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63342 AN: 68030

Other (OTH) AF: 0.915 AC: 1934 AN: 2114

Alfa AF: 0.930 Hom.: 28372

Bravo AF: 0.926

Asia WGS AF: 0.860 AC: 2988 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Nephronophthisis 15 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.31
PhyloP100		-0.91
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: rs897836; hg19: chr11-117252489; COSMIC: COSV107229644; COSMIC: COSV107229644;