chr20-35509524-T-C

Position:

• chr20-35509524-T-C

Variant summary

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

The NM_007186.6(CEP250):​c.7009-474T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,066 control chromosomes in the GnomAD database, including 10,345 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 0.34 (10345 hom., cov: 32)
• Consequence: CEP250 NM_007186.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP250	NM_007186.6	c.7009-474T>C		intron_variant		ENST00000397527.6	NP_009117.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP250	ENST00000397527.6	c.7009-474T>C		intron_variant		5	NM_007186.6	ENSP00000380661.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52047 AN: 151946 Hom.: 10304 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.343 AC: 52152 AN: 152066 Hom.: 10345 Cov.: 32 AF XY: 0.344 AC XY: 25543 AN XY: 74342

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.362

Alfa AF: 0.265 Hom.: 9152

Bravo AF: 0.350

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.48

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: rs2236164; hg19: chr20-34097353;