rs224373

Positions:

• chr20-35491374-G-A
• chr20-35491374-G-C
• chr20-35491374-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007186.6(CEP250):​c.2889+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,567,388 control chromosomes in the GnomAD database, including 20,729 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 0.12 (1434 hom., cov: 31)
  • Exomes 𝑓: 0.16 (19295 hom.)
• Consequence: CEP250 NM_007186.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

Genes affected

CEP250 (HGNC:1859): (centrosomal protein 250) This gene encodes a core centrosomal protein required for centriole-centriole cohesion during interphase of the cell cycle. The encoded protein dissociates from the centrosomes when parental centrioles separate at the beginning of mitosis. The protein associates with and is phosphorylated by NIMA-related kinase 2, which is also associated with the centrosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

CEP250 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP250	NM_007186.6	c.2889+28G>A		intron_variant		ENST00000397527.6	NP_009117.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP250	ENST00000397527.6	c.2889+28G>A		intron_variant		5	NM_007186.6	ENSP00000380661.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18121 AN: 152080 Hom.: 1434 Cov.: 31

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0590

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.158 AC: 223235 AN: 1415190 Hom.: 19295 Cov.: 31 AF XY: 0.157 AC XY: 109848 AN XY: 699592

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.0951

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.000463

Gnomad4 SAS exome AF: 0.0687

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.119 AC: 18118 AN: 152198 Hom.: 1434 Cov.: 31 AF XY: 0.115 AC XY: 8587 AN XY: 74406

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0599

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.142

Alfa AF: 0.161 Hom.: 1419

Bravo AF: 0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs224373; hg19: chr20-34079200;