rs1491225681

Variant names:

• chr5-123386675-TTA-T
• rs1491225681
• NM_001375405.1:c.1431-10_1431-9delTA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001375405.1(CEP120):​c.1431-10_1431-9delTA variant causes a 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.159
• Publications: 0 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 -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 VariationId is 476161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00748 (375/50158) while in subpopulation AFR AF = 0.0136 (208/15290). AF 95% confidence interval is 0.0121. There are 5 homozygotes in GnomAd4. There are 195 alleles in the male GnomAd4 subpopulation. Median coverage is 12. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375405.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP120	NM_001375405.1	MANE Select	c.1431-10_1431-9delTA		intron	N/A	NP_001362334.1	Q8N960-1
	CEP120	NM_153223.4		c.1431-10_1431-9delTA		intron	N/A	NP_694955.2	Q8N960-1
	CEP120	NM_001166226.2		c.1353-10_1353-9delTA		intron	N/A	NP_001159698.1	Q8N960-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP120	ENST00000306467.10	TSL:5 MANE Select	c.1431-10_1431-9delTA		intron	N/A	ENSP00000303058.6	Q8N960-1
	CEP120	ENST00000508138.5	TSL:1	n.*1003-10_*1003-9delTA		intron	N/A	ENSP00000422234.1	D6R8Z4
	CEP120	ENST00000513565.6	TSL:1	n.*641-10_*641-9delTA		intron	N/A	ENSP00000422089.2	Q8N960-3

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

GnomAD2 exomes AF: 0.0475 AC: 889 AN: 18698 AF XY: 0.0471

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0717 AC: 889 AN: 12400

American (AMR) AF: 0.0533 AC: 441 AN: 8280

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 566 AN: 9452

East Asian (EAS) AF: 0.0715 AC: 1339 AN: 18726

South Asian (SAS) AF: 0.0667 AC: 1098 AN: 16462

European-Finnish (FIN) AF: 0.0655 AC: 1473 AN: 22478

Middle Eastern (MID) AF: 0.0883 AC: 180 AN: 2038

European-Non Finnish (NFE) AF: 0.0797 AC: 40914 AN: 513644

Other (OTH) AF: 0.0747 AC: 1939 AN: 25958

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0136 AC: 208 AN: 15290

American (AMR) AF: 0.00109 AC: 5 AN: 4596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1128

East Asian (EAS) AF: 0.000477 AC: 1 AN: 2096

South Asian (SAS) AF: 0.00370 AC: 6 AN: 1620

European-Finnish (FIN) AF: 0.0374 AC: 71 AN: 1900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 70

European-Non Finnish (NFE) AF: 0.00359 AC: 81 AN: 22550

Other (OTH) AF: 0.00482 AC: 3 AN: 622

Alfa AF: 0.00244 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Short-rib thoracic dysplasia 13 with or without polydactyly (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.16
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: rs1491225681; hg19: chr5-122722369; COSMIC: COSV60265411; COSMIC: COSV60265411;