1-243248065-T-G

Position:

• chr1-243248065-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.-42+6975A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 152,278 control chromosomes in the GnomAD database, including 964 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 0.098 (964 hom., cov: 33)
• Consequence: CEP170 NM_014812.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP170	NM_014812.3	c.-42+6975A>C		intron_variant		ENST00000366542.6	NP_055627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP170	ENST00000366542.6	c.-42+6975A>C		intron_variant		5	NM_014812.3	ENSP00000355500	P1

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14931 AN: 152160 Hom.: 964 Cov.: 33

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0933

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

GnomAD4 genome AF: 0.0980 AC: 14930 AN: 152278 Hom.: 964 Cov.: 33 AF XY: 0.0976 AC XY: 7270 AN XY: 74456

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0583

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.110 Hom.: 542

Bravo AF: 0.0924

Asia WGS AF: 0.0620 AC: 215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.49

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: rs10926977; hg19: chr1-243411367;