rs61737637

chr11-117394388-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014956.5(CEP164):c.2655C>T(p.Thr885=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000711 in 1,610,564 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (5 hom.)
• Consequence: CEP164 NM_014956.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.06

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-117394388-C-T is Benign according to our data. Variant chr11-117394388-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117394388-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-5.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00383 (583/152312) while in subpopulation AFR AF= 0.0135 (563/41564). AF 95% confidence interval is 0.0126. There are 5 homozygotes in gnomad4. There are 280 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP164	NM_014956.5	c.2655C>T	p.Thr885=	synonymous_variant	21/33	ENST00000278935.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP164	ENST00000278935.8	c.2655C>T	p.Thr885=	synonymous_variant	21/33	1	NM_014956.5	P1
CEP164	ENST00000533223.1	n.3537C>T		non_coding_transcript_exon_variant	7/16	1
CEP164	ENST00000533675.5	n.2763C>T		non_coding_transcript_exon_variant	16/27	2
CEP164	ENST00000533706.5	n.1979C>T		non_coding_transcript_exon_variant	14/27	5

Frequencies

GnomAD3 genomes AF: 0.00383 AC: 583 AN: 152194 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000796 AC: 193 AN: 242340 Hom.: 0 AF XY: 0.000595 AC XY: 78 AN XY: 131090

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.000238

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000338

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000548

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.000385 AC: 562 AN: 1458252 Hom.: 5 Cov.: 31 AF XY: 0.000328 AC XY: 238 AN XY: 724994

Gnomad4 AFR exome AF: 0.0138

Gnomad4 AMR exome AF: 0.000272

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000468

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000297

Gnomad4 OTH exome AF: 0.000813

GnomAD4 genome AF: 0.00383 AC: 583 AN: 152312 Hom.: 5 Cov.: 32 AF XY: 0.00376 AC XY: 280 AN XY: 74474

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00193 Hom.: 2

Bravo AF: 0.00395

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Nephronophthisis 15 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 31, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.011
Dann	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs61737637; hg19: chr11-117265104;