1-243227829-T-G

Variant summary

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

The NM_014812.3(CEP170):c.-41-2508A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,206 control chromosomes in the GnomAD database, including 55,690 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 0.85 (55690 hom., cov: 32)
• Consequence: CEP170 NM_014812.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

Genes affected

CEP170 (HGNC:28920): (centrosomal protein 170) The product of this gene is a component of the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. During interphase, the encoded protein localizes to the sub-distal appendages of mature centrioles, which are microtubule-based structures thought to help organize centrosomes. During mitosis, the protein associates with spindle microtubules near the centrosomes. The protein interacts with and is phosphorylated by polo-like kinase 1, and functions in maintaining microtubule organization and cell morphology. The human genome contains a putative transcribed pseudogene. Several alternatively spliced transcript variants of this gene have been found, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP170	NM_014812.3	c.-41-2508A>C		intron_variant		ENST00000366542.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP170	ENST00000366542.6	c.-41-2508A>C		intron_variant		5	NM_014812.3	P1

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129935 AN: 152090 Hom.: 55660 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.873

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

GnomAD4 genome AF: 0.854 AC: 130018 AN: 152206 Hom.: 55690 Cov.: 32 AF XY: 0.856 AC XY: 63720 AN XY: 74424

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.873

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.875

Alfa AF: 0.875 Hom.: 76427

Bravo AF: 0.852

Asia WGS AF: 0.928 AC: 3227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.30
Dann	Benign	0.59

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: rs4658547; hg19: chr1-243391131;