1-243127340-G-A

Position:

• chr1-243127340-G-A

Variant summary

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

The NM_014812.3(CEP170):​c.4466-602C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,148 control chromosomes in the GnomAD database, including 2,002 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 0.10 (2002 hom., cov: 31)
• Consequence: CEP170 NM_014812.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP170	NM_014812.3	c.4466-602C>T		intron_variant		ENST00000366542.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP170	ENST00000366542.6	c.4466-602C>T		intron_variant		5	NM_014812.3	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15763 AN: 152030 Hom.: 1996 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0580

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00457

Gnomad OTH AF: 0.0768

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

GnomAD4 genome AF: 0.104 AC: 15801 AN: 152148 Hom.: 2002 Cov.: 31 AF XY: 0.105 AC XY: 7801 AN XY: 74392

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.0570

Gnomad4 FIN AF: 0.0492

Gnomad4 NFE AF: 0.00457

Gnomad4 OTH AF: 0.0774

Alfa AF: 0.0492 Hom.: 188

Bravo AF: 0.119

Asia WGS AF: 0.151 AC: 526 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	1.2
DANN	Benign	0.45

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: rs2105146; hg19: chr1-243290642;