20-35509524-T-C

Variant names:

• chr20-35509524-T-C
• rs2236164
• NM_007186.6:c.7009-474T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 publications found

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 Gene-Disease associations (from GenCC):

• cone-rod dystrophy and hearing loss 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: NO_KNOWN Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007186.6. 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
	CEP250	NM_007186.6	MANE Select	c.7009-474T>C		intron	N/A	NP_009117.2
	CEP250	NM_001318219.1		c.5113-474T>C		intron	N/A	NP_001305148.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP250	ENST00000397527.6	TSL:5 MANE Select	c.7009-474T>C		intron	N/A	ENSP00000380661.1
	CEP250	ENST00000706828.1		c.7180-474T>C		intron	N/A	ENSP00000516576.1
	CEP250	ENST00000937927.1		c.6988-474T>C		intron	N/A	ENSP00000607986.1

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

African (AFR) AF: 0.544 AC: 22535 AN: 41434

American (AMR) AF: 0.307 AC: 4687 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1444 AN: 5160

South Asian (SAS) AF: 0.498 AC: 2403 AN: 4828

European-Finnish (FIN) AF: 0.221 AC: 2337 AN: 10576

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16428 AN: 67996

Other (OTH) AF: 0.362 AC: 765 AN: 2114

Alfa AF: 0.276 Hom.: 23465

Bravo AF: 0.350

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.48
PhyloP100		0.082
PromoterAI		0.012	Neutral
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: rs2236164; hg19: chr20-34097353;