rs200103555

Positions:

• chr11-117396185-GCTGGGGGCTGGGGC-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_014956.5(CEP164):​c.3216+20_3216+33del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 1,610,816 control chromosomes in the GnomAD database, including 668 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (37 hom., cov: 28)
  • Exomes 𝑓: 0.021 (631 hom.)
• Consequence: CEP164 NM_014956.5 splice_donor_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-117396185-GCTGGGGGCTGGGGC-G is Benign according to our data. Variant chr11-117396185-GCTGGGGGCTGGGGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 473083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117396185-GCTGGGGGCTGGGGC-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0165 (2506/152054) while in subpopulation NFE AF= 0.0253 (1721/67968). AF 95% confidence interval is 0.0243. There are 37 homozygotes in gnomad4. There are 1183 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP164	NM_014956.5	c.3216+20_3216+33del		splice_donor_region_variant, intron_variant		ENST00000278935.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP164	ENST00000278935.8	c.3216+20_3216+33del		splice_donor_region_variant, intron_variant		1	NM_014956.5	P1
CEP164	ENST00000533223.1	n.4098+20_4098+33del		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		1
CEP164	ENST00000533675.5	n.3443+20_3443+33del		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		2
CEP164	ENST00000533706.5	n.2540+20_2540+33del		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2508 AN: 151940 Hom.: 37 Cov.: 28

Gnomad AFR AF: 0.00435

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0159

GnomAD3 exomes AF: 0.0175 AC: 4316 AN: 247082 Hom.: 59 AF XY: 0.0172 AC XY: 2323 AN XY: 134672

Gnomad AFR exome AF: 0.00354

Gnomad AMR exome AF: 0.0175

Gnomad ASJ exome AF: 0.0199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00223

Gnomad FIN exome AF: 0.0226

Gnomad NFE exome AF: 0.0250

Gnomad OTH exome AF: 0.0226

GnomAD4 exome AF: 0.0208 AC: 30292 AN: 1458762 Hom.: 631 AF XY: 0.0205 AC XY: 14890 AN XY: 725750

Gnomad4 AFR exome AF: 0.00332

Gnomad4 AMR exome AF: 0.0173

Gnomad4 ASJ exome AF: 0.0211

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00237

Gnomad4 FIN exome AF: 0.0236

Gnomad4 NFE exome AF: 0.0236

Gnomad4 OTH exome AF: 0.0198

GnomAD4 genome AF: 0.0165 AC: 2506 AN: 152054 Hom.: 37 Cov.: 28 AF XY: 0.0159 AC XY: 1183 AN XY: 74318

Gnomad4 AFR AF: 0.00434

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0253

Gnomad4 OTH AF: 0.0157

Alfa AF: 0.0215 Hom.: 14

Bravo AF: 0.0159

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0250

EpiControl AF: 0.0251

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Nephronophthisis 15 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Feb 02, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200103555; hg19: chr11-117266901;