rs573801

Variant names:

• chr11-117338552-C-T
• rs573801
• NM_014956.5:c.-21-14C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-117338552-C-T
• chr11-117338552-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014956.5(CEP164):​c.-21-14C>T variant causes a 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.08
• Publications: 7 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 -20 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 VariationId is 1245048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 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.-21-14C>T		intron	N/A	NP_055771.4
	CEP164	NM_001440949.1		c.-21-14C>T		intron	N/A	NP_001427878.1
	CEP164	NM_001440950.1		c.-21-14C>T		intron	N/A	NP_001427879.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	ENST00000278935.8	TSL:1 MANE Select	c.-21-14C>T		intron	N/A	ENSP00000278935.3	Q9UPV0-1
	CEP164	ENST00000533570.1	TSL:1	c.-21-14C>T		intron	N/A	ENSP00000431302.1	E9PLS8
	CEP164	ENST00000527609.5	TSL:1	c.-21-14C>T		intron	N/A	ENSP00000436351.2	E9PLS8

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

GnomAD2 exomes AF: 0.224 AC: 56265 AN: 250640 AF XY: 0.222

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 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

African (AFR) AF: 0.278 AC: 9059 AN: 32624

American (AMR) AF: 0.300 AC: 13366 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6882 AN: 25812

East Asian (EAS) AF: 0.126 AC: 4964 AN: 39500

South Asian (SAS) AF: 0.255 AC: 21759 AN: 85406

European-Finnish (FIN) AF: 0.154 AC: 8217 AN: 53366

Middle Eastern (MID) AF: 0.270 AC: 1533 AN: 5688

European-Non Finnish (NFE) AF: 0.217 AC: 233294 AN: 1075604

Other (OTH) AF: 0.227 AC: 13379 AN: 58952

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

African (AFR) AF: 0.277 AC: 11500 AN: 41468

American (AMR) AF: 0.266 AC: 4067 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3470

East Asian (EAS) AF: 0.137 AC: 708 AN: 5156

South Asian (SAS) AF: 0.244 AC: 1175 AN: 4818

European-Finnish (FIN) AF: 0.148 AC: 1566 AN: 10598

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14112 AN: 67976

Other (OTH) AF: 0.222 AC: 467 AN: 2108

Alfa AF: 0.224 Hom.: 842

Bravo AF: 0.241

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.66
PhyloP100		1.1
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: rs573801; hg19: chr11-117209268; COSMIC: COSV54041405; COSMIC: COSV54041405;