rs1491225681

Positions:

• chr5-123386675-TTA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001375405.1(CEP120):​c.1431-10_1431-9del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 679,596 control chromosomes in the GnomAD database, including 363 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (5 hom., cov: 12)
  • Exomes 𝑓: 0.078 (358 hom.)
• Consequence: CEP120 NM_001375405.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.159

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 5-123386675-TTA-T is Benign according to our data. Variant chr5-123386675-TTA-T is described in ClinVar as [Benign]. Clinvar id is 476161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123386675-TTA-T is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP120	NM_001375405.1	c.1431-10_1431-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000306467.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP120	ENST00000306467.10	c.1431-10_1431-9del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001375405.1	P1

Frequencies

GnomAD3 genomes AF: 0.00748 AC: 375 AN: 50158 Hom.: 5 Cov.: 12

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000475

Gnomad SAS AF: 0.00366

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00359

Gnomad OTH AF: 0.00482

GnomAD3 exomes AF: 0.0475 AC: 889 AN: 18698 Hom.: 130 AF XY: 0.0471 AC XY: 466 AN XY: 9904

Gnomad AFR exome AF: 0.0289

Gnomad AMR exome AF: 0.0318

Gnomad ASJ exome AF: 0.0545

Gnomad EAS exome AF: 0.0446

Gnomad SAS exome AF: 0.0370

Gnomad FIN exome AF: 0.0407

Gnomad NFE exome AF: 0.0566

Gnomad OTH exome AF: 0.0521

GnomAD4 exome AF: 0.0776 AC: 48839 AN: 629438 Hom.: 358 AF XY: 0.0768 AC XY: 23480 AN XY: 305718

Gnomad4 AFR exome AF: 0.0717

Gnomad4 AMR exome AF: 0.0533

Gnomad4 ASJ exome AF: 0.0599

Gnomad4 EAS exome AF: 0.0715

Gnomad4 SAS exome AF: 0.0667

Gnomad4 FIN exome AF: 0.0655

Gnomad4 NFE exome AF: 0.0797

Gnomad4 OTH exome AF: 0.0747

GnomAD4 genome AF: 0.00748 AC: 375 AN: 50158 Hom.: 5 Cov.: 12 AF XY: 0.00823 AC XY: 195 AN XY: 23696

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.00109

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000477

Gnomad4 SAS AF: 0.00370

Gnomad4 FIN AF: 0.0374

Gnomad4 NFE AF: 0.00359

Gnomad4 OTH AF: 0.00482

Alfa AF: 0.00244 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Short-rib thoracic dysplasia 13 with or without polydactyly Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs1491225681; hg19: chr5-122722369; COSMIC: COSV60265411; COSMIC: COSV60265411;