chr1-243127340-G-A

Variant names:

• chr1-243127340-G-A
• rs2105146
• NM_014812.3:c.4466-602C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

ENSG00000227230 (HGNC:):

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 = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP170	NM_014812.3	c.4466-602C>T		intron_variant	Intron 19 of 19	ENST00000366542.6	NP_055627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP170	ENST00000366542.6	c.4466-602C>T		intron_variant	Intron 19 of 19	5	NM_014812.3	ENSP00000355500.1
CEP170	ENST00000366544.6	c.4172-602C>T		intron_variant	Intron 18 of 18	5		ENSP00000355502.1
CEP170	ENST00000366543.5	c.4094-602C>T		intron_variant	Intron 18 of 18	5		ENSP00000355501.1

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

African (AFR) AF: 0.289 AC: 11982 AN: 41442

American (AMR) AF: 0.102 AC: 1562 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.182 AC: 940 AN: 5158

South Asian (SAS) AF: 0.0570 AC: 275 AN: 4822

European-Finnish (FIN) AF: 0.0492 AC: 522 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00457 AC: 311 AN: 68034

Other (OTH) AF: 0.0774 AC: 163 AN: 2106

Alfa AF: 0.0460 Hom.: 1348

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
PhyloP100		-0.29
Mutation Taster		=99/1	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: rs2105146; hg19: chr1-243290642;