chr11-117396038-A-C

Variant names:

• chr11-117396038-A-C
• rs693147
• NM_014956.5:c.3090-16A>C

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.3090-16A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 1,613,544 control chromosomes in the GnomAD database, including 292,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27686 hom., cov: 32)
  • Exomes 𝑓: 0.60 (264476 hom.)
• Consequence: CEP164 NM_014956.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.03
• Publications: 12 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=-0.91).
• BP6: Variant 11-117396038-A-C is Benign according to our data. Variant chr11-117396038-A-C is described in ClinVar as Benign. ClinVar VariationId is 260483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 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.3090-16A>C		intron	N/A	NP_055771.4
	CEP164	NM_001440949.1		c.3099-19A>C		intron	N/A	NP_001427878.1
	CEP164	NM_001440950.1		c.3090-16A>C		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.3090-16A>C		intron	N/A	ENSP00000278935.3	Q9UPV0-1
	CEP164	ENST00000533223.1	TSL:1	n.3972-16A>C		intron	N/A
	CEP164	ENST00000957770.1		c.3021-16A>C		intron	N/A	ENSP00000627829.1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90669 AN: 151832 Hom.: 27648 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.602

GnomAD2 exomes AF: 0.539 AC: 135269 AN: 251188 AF XY: 0.545

Gnomad AFR exome AF: 0.651

Gnomad AMR exome AF: 0.292

Gnomad ASJ exome AF: 0.554

Gnomad EAS exome AF: 0.345

Gnomad FIN exome AF: 0.599

Gnomad NFE exome AF: 0.628

Gnomad OTH exome AF: 0.544

GnomAD4 exome AF: 0.597 AC: 872013 AN: 1461594 Hom.: 264476 Cov.: 55 AF XY: 0.595 AC XY: 432436 AN XY: 727114

African (AFR) AF: 0.651 AC: 21788 AN: 33472

American (AMR) AF: 0.312 AC: 13935 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 14519 AN: 26130

East Asian (EAS) AF: 0.388 AC: 15394 AN: 39692

South Asian (SAS) AF: 0.493 AC: 42495 AN: 86210

European-Finnish (FIN) AF: 0.594 AC: 31730 AN: 53400

Middle Eastern (MID) AF: 0.538 AC: 3103 AN: 5764

European-Non Finnish (NFE) AF: 0.624 AC: 694149 AN: 1111838

Other (OTH) AF: 0.578 AC: 34900 AN: 60378

GnomAD4 genome AF: 0.597 AC: 90754 AN: 151950 Hom.: 27686 Cov.: 32 AF XY: 0.590 AC XY: 43830 AN XY: 74278

African (AFR) AF: 0.648 AC: 26867 AN: 41442

American (AMR) AF: 0.430 AC: 6577 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1980 AN: 3470

East Asian (EAS) AF: 0.358 AC: 1837 AN: 5132

South Asian (SAS) AF: 0.490 AC: 2354 AN: 4808

European-Finnish (FIN) AF: 0.583 AC: 6150 AN: 10554

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

European-Non Finnish (NFE) AF: 0.632 AC: 42969 AN: 67946

Other (OTH) AF: 0.604 AC: 1276 AN: 2112

Alfa AF: 0.614 Hom.: 30563

Bravo AF: 0.587

Asia WGS AF: 0.458 AC: 1593 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Nephronophthisis 15 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.42
PhyloP100		-1.0
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: rs693147; hg19: chr11-117266754; COSMIC: COSV54042087; COSMIC: COSV54042087;