rs2115172

Variant names:

• chr5-123349434-A-G
• rs2115172
• NM_001375405.1:c.2726+510T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375405.1(CEP120):​c.2726+510T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,952 control chromosomes in the GnomAD database, including 12,779 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (12779 hom., cov: 32)
• Consequence: CEP120 NM_001375405.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP120	NM_001375405.1	c.2726+510T>C		intron_variant	Intron 19 of 19	ENST00000306467.10	NP_001362334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP120	ENST00000306467.10	c.2726+510T>C		intron_variant	Intron 19 of 19	5	NM_001375405.1	ENSP00000303058.6

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62170 AN: 151834 Hom.: 12772 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.437

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.409 AC: 62201 AN: 151952 Hom.: 12779 Cov.: 32 AF XY: 0.410 AC XY: 30473 AN XY: 74274

African (AFR) AF: 0.344 AC: 14257 AN: 41428

American (AMR) AF: 0.418 AC: 6375 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1298 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2459 AN: 5154

South Asian (SAS) AF: 0.469 AC: 2264 AN: 4824

European-Finnish (FIN) AF: 0.450 AC: 4751 AN: 10556

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29450 AN: 67940

Other (OTH) AF: 0.438 AC: 924 AN: 2110

Alfa AF: 0.412 Hom.: 5299

Bravo AF: 0.406

Asia WGS AF: 0.480 AC: 1665 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.84
PhyloP100		0.40
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: rs2115172; hg19: chr5-122685128;