rs4938369

Variant names:

• chr11-117317404-C-T
• rs4938369
• ENST00000525734.5:c.-98+2676C>T

Variant summary

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

The ENST00000525734.5(CEP164):​c.-98+2676C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 152,074 control chromosomes in the GnomAD database, including 601 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 0.075 (601 hom., cov: 32)
• Consequence: CEP164 ENST00000525734.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715
• Publications: 5 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

ENSG00000250699 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP164	ENST00000525734.5	c.-98+2676C>T		intron_variant	Intron 1 of 4	2		ENSP00000436609.1
ENSG00000250699	ENST00000504906.1	n.342-896G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11347 AN: 151956 Hom.: 602 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0805

Gnomad OTH AF: 0.0679

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0747 AC: 11354 AN: 152074 Hom.: 601 Cov.: 32 AF XY: 0.0789 AC XY: 5865 AN XY: 74326

African (AFR) AF: 0.0176 AC: 729 AN: 41494

American (AMR) AF: 0.134 AC: 2048 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3472

East Asian (EAS) AF: 0.168 AC: 867 AN: 5160

South Asian (SAS) AF: 0.0885 AC: 425 AN: 4804

European-Finnish (FIN) AF: 0.139 AC: 1472 AN: 10574

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0805 AC: 5475 AN: 68002

Other (OTH) AF: 0.0677 AC: 143 AN: 2112

Alfa AF: 0.459 Hom.: 6701

Bravo AF: 0.0750

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.96
DANN	Benign	0.74
PhyloP100		-0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4938369; hg19: chr11-117188120;