rs224373

Variant names:

• chr20-35491374-G-A
• rs224373
• NM_007186.6:c.2889+28G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP250	NM_007186.6	MANE Select	c.2889+28G>A		intron	N/A	NP_009117.2
	CEP250	NM_001318219.1		c.993+28G>A		intron	N/A	NP_001305148.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP250	ENST00000397527.6	TSL:5 MANE Select	c.2889+28G>A		intron	N/A	ENSP00000380661.1
	CEP250	ENST00000706828.1		c.3060+28G>A		intron	N/A	ENSP00000516576.1
	CEP250	ENST00000706829.1		c.2889+28G>A		intron	N/A	ENSP00000516577.1

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

African (AFR) AF: 0.0256 AC: 821 AN: 32102

American (AMR) AF: 0.0951 AC: 3589 AN: 37752

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6306 AN: 25324

East Asian (EAS) AF: 0.000463 AC: 17 AN: 36694

South Asian (SAS) AF: 0.0687 AC: 5535 AN: 80532

European-Finnish (FIN) AF: 0.140 AC: 7093 AN: 50486

Middle Eastern (MID) AF: 0.161 AC: 918 AN: 5708

European-Non Finnish (NFE) AF: 0.175 AC: 190193 AN: 1087896

Other (OTH) AF: 0.149 AC: 8763 AN: 58696

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

African (AFR) AF: 0.0294 AC: 1220 AN: 41556

American (AMR) AF: 0.114 AC: 1740 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5182

South Asian (SAS) AF: 0.0599 AC: 289 AN: 4824

European-Finnish (FIN) AF: 0.128 AC: 1357 AN: 10596

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12099 AN: 67968

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.156 Hom.: 1795

Bravo AF: 0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs224373; hg19: chr20-34079200;