11-117390772-C-G

Variant names:

• chr11-117390772-C-G
• rs897837
• NM_014956.5:c.1935-5C>G

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.1935-5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,613,500 control chromosomes in the GnomAD database, including 22,936 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1525 hom., cov: 31)
  • Exomes 𝑓: 0.17 (21411 hom.)
• Consequence: CEP164 NM_014956.5 splice_region, intron
• Scores: Splicing: ADA: 0.0005488
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.655
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-117390772-C-G is Benign according to our data. Variant chr11-117390772-C-G is described in ClinVar as Benign. ClinVar VariationId is 260476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	NM_014956.5	MANE Select	c.1935-5C>G		splice_region intron	N/A	NP_055771.4
	CEP164	NM_001440949.1		c.1944-5C>G		splice_region intron	N/A	NP_001427878.1
	CEP164	NM_001440950.1		c.1935-5C>G		splice_region intron	N/A	NP_001427879.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	ENST00000278935.8	TSL:1 MANE Select	c.1935-5C>G		splice_region intron	N/A	ENSP00000278935.3
	CEP164	ENST00000533223.1	TSL:1	n.2817-5C>G		splice_region intron	N/A
	CEP164	ENST00000529153.5	TSL:4	n.384-5C>G		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19367 AN: 151866 Hom.: 1524 Cov.: 31

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.0973

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.134

GnomAD2 exomes AF: 0.169 AC: 42588 AN: 251290 AF XY: 0.170

Gnomad AFR exome AF: 0.0294

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.124

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.167 AC: 243902 AN: 1461516 Hom.: 21411 Cov.: 33 AF XY: 0.168 AC XY: 122187 AN XY: 727086

African (AFR) AF: 0.0292 AC: 977 AN: 33468

American (AMR) AF: 0.255 AC: 11406 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5142 AN: 26130

East Asian (EAS) AF: 0.115 AC: 4546 AN: 39700

South Asian (SAS) AF: 0.201 AC: 17304 AN: 86236

European-Finnish (FIN) AF: 0.146 AC: 7776 AN: 53404

Middle Eastern (MID) AF: 0.186 AC: 1069 AN: 5748

European-Non Finnish (NFE) AF: 0.168 AC: 186240 AN: 1111748

Other (OTH) AF: 0.156 AC: 9442 AN: 60370

GnomAD4 genome AF: 0.127 AC: 19371 AN: 151984 Hom.: 1525 Cov.: 31 AF XY: 0.129 AC XY: 9555 AN XY: 74266

African (AFR) AF: 0.0331 AC: 1373 AN: 41482

American (AMR) AF: 0.196 AC: 2988 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3470

East Asian (EAS) AF: 0.126 AC: 648 AN: 5142

South Asian (SAS) AF: 0.184 AC: 884 AN: 4808

European-Finnish (FIN) AF: 0.138 AC: 1458 AN: 10550

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.161 AC: 10968 AN: 67958

Other (OTH) AF: 0.133 AC: 281 AN: 2114

Alfa AF: 0.156 Hom.: 660

Bravo AF: 0.130

Asia WGS AF: 0.130 AC: 450 AN: 3478

EpiCase AF: 0.162

EpiControl AF: 0.157

ClinVar

ClinVar submissions as Germline

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	-0.83
CADD	Benign	3.7
DANN	Benign	0.34
PhyloP100		0.66
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00055
dbscSNV1_RF	Benign	0.070
SpliceAI score (max)		0.010		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: rs897837; hg19: chr11-117261488; COSMIC: COSV54038326;