ENST00000508138.5:n.*2592A>C

Variant names:

• chr5-123346460-T-G
• rs2303719
• ENST00000508138.5:n.*2592A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000508138.5(CEP120):​n.*2592A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,299,740 control chromosomes in the GnomAD database, including 314,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (36018 hom., cov: 32)
  • Exomes 𝑓: 0.70 (278418 hom.)
• Consequence: CEP120 ENST00000508138.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.129
• Publications: 7 publications found

Genes affected

CEP120 (HGNC:26690): (centrosomal protein 120) This gene encodes a protein that functions in the microtubule-dependent coupling of the nucleus and the centrosome. A similar protein in mouse plays a role in both interkinetic nuclear migration, which is a characteristic pattern of nuclear movement in neural progenitors, and in neural progenitor self-renewal. Mutations in this gene are predicted to result in neurogenic defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

CEP120 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Joubert syndrome 31

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• short-rib thoracic dysplasia 13 with or without polydactyly

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with ocular defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-123346460-T-G is Benign according to our data. Variant chr5-123346460-T-G is described in ClinVar as [Benign]. Clinvar id is 1248158.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP120	NM_001375405.1	c.*59A>C		3_prime_UTR_variant	Exon 20 of 20	ENST00000306467.10	NP_001362334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP120	ENST00000306467.10	c.*59A>C		3_prime_UTR_variant	Exon 20 of 20	5	NM_001375405.1	ENSP00000303058.6

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104338 AN: 151882 Hom.: 35990 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.724

GnomAD4 exome AF: 0.695 AC: 797685 AN: 1147740 Hom.: 278418 Cov.: 14 AF XY: 0.694 AC XY: 399866 AN XY: 575848

African (AFR) AF: 0.646 AC: 16706 AN: 25854

American (AMR) AF: 0.645 AC: 17622 AN: 27332

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 14515 AN: 20034

East Asian (EAS) AF: 0.548 AC: 20394 AN: 37242

South Asian (SAS) AF: 0.662 AC: 43510 AN: 65700

European-Finnish (FIN) AF: 0.711 AC: 34388 AN: 48366

Middle Eastern (MID) AF: 0.744 AC: 3678 AN: 4944

European-Non Finnish (NFE) AF: 0.705 AC: 612806 AN: 869312

Other (OTH) AF: 0.696 AC: 34066 AN: 48956

GnomAD4 genome AF: 0.687 AC: 104416 AN: 152000 Hom.: 36018 Cov.: 32 AF XY: 0.684 AC XY: 50819 AN XY: 74270

African (AFR) AF: 0.651 AC: 26986 AN: 41442

American (AMR) AF: 0.702 AC: 10706 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2555 AN: 3470

East Asian (EAS) AF: 0.574 AC: 2969 AN: 5172

South Asian (SAS) AF: 0.665 AC: 3204 AN: 4818

European-Finnish (FIN) AF: 0.708 AC: 7469 AN: 10548

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48118 AN: 67982

Other (OTH) AF: 0.726 AC: 1534 AN: 2112

Alfa AF: 0.700 Hom.: 77899

Bravo AF: 0.687

Asia WGS AF: 0.657 AC: 2282 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.8
DANN	Benign	0.72
PhyloP100		0.13
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: rs2303719; hg19: chr5-122682154;