rs1261791

Variant names:

• chr11-117329922-T-A
• rs1261791
• NM_014956.5:c.-98+2018T>A

Variant summary

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

The NM_014956.5(CEP164):​c.-98+2018T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 146,676 control chromosomes in the GnomAD database, including 1,010 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 0.098 (1010 hom., cov: 28)
• Consequence: CEP164 NM_014956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 2 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 = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP164	NM_014956.5	c.-98+2018T>A		intron_variant	Intron 1 of 32	ENST00000278935.8	NP_055771.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP164	ENST00000278935.8	c.-98+2018T>A		intron_variant	Intron 1 of 32	1	NM_014956.5	ENSP00000278935.3

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14352 AN: 146576 Hom.: 1006 Cov.: 28

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.0557

Gnomad ASJ AF: 0.0898

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.0795

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0924

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

GnomAD4 genome AF: 0.0981 AC: 14385 AN: 146676 Hom.: 1010 Cov.: 28 AF XY: 0.0972 AC XY: 6904 AN XY: 71036

African (AFR) AF: 0.201 AC: 7917 AN: 39448

American (AMR) AF: 0.0557 AC: 778 AN: 13976

Ashkenazi Jewish (ASJ) AF: 0.0898 AC: 311 AN: 3464

East Asian (EAS) AF: 0.0224 AC: 111 AN: 4960

South Asian (SAS) AF: 0.0693 AC: 321 AN: 4630

European-Finnish (FIN) AF: 0.0444 AC: 423 AN: 9528

Middle Eastern (MID) AF: 0.0755 AC: 21 AN: 278

European-Non Finnish (NFE) AF: 0.0614 AC: 4145 AN: 67458

Other (OTH) AF: 0.0916 AC: 186 AN: 2030

Alfa AF: 0.0855 Hom.: 87

Bravo AF: 0.103

Asia WGS AF: 0.0700 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.70
PhyloP100		-0.0030
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: rs1261791; hg19: chr11-117200638;