1-243248065-T-G

Variant names:

• chr1-243248065-T-G
• rs10926977
• NM_014812.3:c.-42+6975A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014812.3. 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
	CEP170	NM_014812.3	MANE Select	c.-42+6975A>C		intron	N/A	NP_055627.2
	CEP170	NM_001042404.2		c.-42+6975A>C		intron	N/A	NP_001035863.1
	CEP170	NM_001042405.2		c.-42+6975A>C		intron	N/A	NP_001035864.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP170	ENST00000366542.6	TSL:5 MANE Select	c.-42+6975A>C		intron	N/A	ENSP00000355500.1
	CEP170	ENST00000366544.6	TSL:5	c.-42+6975A>C		intron	N/A	ENSP00000355502.1
	CEP170	ENST00000366543.5	TSL:5	c.-42+6975A>C		intron	N/A	ENSP00000355501.1

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

African (AFR) AF: 0.0273 AC: 1136 AN: 41578

American (AMR) AF: 0.109 AC: 1673 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3472

East Asian (EAS) AF: 0.0583 AC: 302 AN: 5184

South Asian (SAS) AF: 0.107 AC: 517 AN: 4824

European-Finnish (FIN) AF: 0.127 AC: 1348 AN: 10588

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9175 AN: 68016

Other (OTH) AF: 0.0919 AC: 194 AN: 2112

Alfa AF: 0.111 Hom.: 603

Bravo AF: 0.0924

Asia WGS AF: 0.0620 AC: 215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.49
PhyloP100		-0.18
Mutation Taster		=100/0	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: rs10926977; hg19: chr1-243411367;