1-243136134-T-A

Variant names:

• chr1-243136134-T-A
• rs12047774
• NM_014812.3:c.4319+9A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014812.3(CEP170):​c.4319+9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 1,450,766 control chromosomes in the GnomAD database, including 2,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (243 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1989 hom.)
• Consequence: CEP170 NM_014812.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.385
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-243136134-T-A is Benign according to our data. Variant chr1-243136134-T-A is described in ClinVar as [Benign]. Clinvar id is 770336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP170	NM_014812.3	c.4319+9A>T		intron_variant	Intron 17 of 19	ENST00000366542.6	NP_055627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP170	ENST00000366542.6	c.4319+9A>T		intron_variant	Intron 17 of 19	5	NM_014812.3	ENSP00000355500.1
CEP170	ENST00000366544.6	c.4025+9A>T		intron_variant	Intron 16 of 18	5		ENSP00000355502.1
CEP170	ENST00000366543.5	c.3947+9A>T		intron_variant	Intron 16 of 18	5		ENSP00000355501.1

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12852 AN: 151660 Hom.: 243 Cov.: 32

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0965

Gnomad ASJ AF: 0.0719

Gnomad EAS AF: 0.0621

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0779

GnomAD2 exomes AF: 0.0976 AC: 11439 AN: 117160 AF XY: 0.0979

Gnomad AFR exome AF: 0.0206

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.0652

Gnomad EAS exome AF: 0.0584

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.101 AC: 131043 AN: 1298988 Hom.: 1989 Cov.: 24 AF XY: 0.101 AC XY: 64782 AN XY: 643636

African (AFR) AF: 0.0158 AC: 446 AN: 28158

American (AMR) AF: 0.112 AC: 2539 AN: 22700

Ashkenazi Jewish (ASJ) AF: 0.0667 AC: 1530 AN: 22922

East Asian (EAS) AF: 0.0453 AC: 1596 AN: 35204

South Asian (SAS) AF: 0.0878 AC: 6275 AN: 71436

European-Finnish (FIN) AF: 0.113 AC: 5513 AN: 48678

Middle Eastern (MID) AF: 0.0447 AC: 244 AN: 5464

European-Non Finnish (NFE) AF: 0.107 AC: 108106 AN: 1010014

Other (OTH) AF: 0.0881 AC: 4794 AN: 54412

GnomAD4 genome AF: 0.0846 AC: 12846 AN: 151778 Hom.: 243 Cov.: 32 AF XY: 0.0847 AC XY: 6287 AN XY: 74192

African (AFR) AF: 0.0219 AC: 911 AN: 41526

American (AMR) AF: 0.0963 AC: 1467 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0719 AC: 249 AN: 3462

East Asian (EAS) AF: 0.0621 AC: 322 AN: 5188

South Asian (SAS) AF: 0.0947 AC: 455 AN: 4806

European-Finnish (FIN) AF: 0.116 AC: 1227 AN: 10536

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.117 AC: 7895 AN: 67720

Other (OTH) AF: 0.0766 AC: 161 AN: 2102

Alfa AF: 0.0606 Hom.: 21

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 30, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.69
PhyloP100		-0.39
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: rs12047774; hg19: chr1-243299436; COSMIC: COSV60509555; COSMIC: COSV60509555;