rs2028414

chr14-104883051-A-Cchr14-104883051-A-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001112726.3(CEP170B):c.594A>C(p.Pro198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,529,066 control chromosomes in the GnomAD database, including 306,830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (27392 hom., cov: 27)
  • Exomes 𝑓: 0.63 (279438 hom.)
• Consequence: CEP170B NM_001112726.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.83

Genes affected

CEP170B (HGNC:20362): (centrosomal protein 170B) Predicted to be located in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 14-104883051-A-C is Benign according to our data. Variant chr14-104883051-A-C is described in ClinVar as [Benign]. Clinvar id is 3058875.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP170B	NM_001112726.3	c.594A>C	p.Pro198=	synonymous_variant	8/19	ENST00000414716.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP170B	ENST00000414716.8	c.594A>C	p.Pro198=	synonymous_variant	8/19	1	NM_001112726.3	P1
CEP170B	ENST00000556508.5	c.384A>C	p.Pro128=	synonymous_variant	7/18	5

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89474 AN: 150994 Hom.: 27392 Cov.: 27

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.626

GnomAD3 exomes AF: 0.578 AC: 84752 AN: 146532 Hom.: 25823 AF XY: 0.586 AC XY: 47002 AN XY: 80140

Gnomad AFR exome AF: 0.498

Gnomad AMR exome AF: 0.527

Gnomad ASJ exome AF: 0.703

Gnomad EAS exome AF: 0.202

Gnomad SAS exome AF: 0.623

Gnomad FIN exome AF: 0.663

Gnomad NFE exome AF: 0.641

Gnomad OTH exome AF: 0.610

GnomAD4 exome AF: 0.631 AC: 869874 AN: 1377952 Hom.: 279438 Cov.: 64 AF XY: 0.631 AC XY: 428088 AN XY: 678104

Gnomad4 AFR exome AF: 0.505

Gnomad4 AMR exome AF: 0.542

Gnomad4 ASJ exome AF: 0.700

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.620

Gnomad4 FIN exome AF: 0.658

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.620

GnomAD4 genome AF: 0.592 AC: 89504 AN: 151114 Hom.: 27392 Cov.: 27 AF XY: 0.590 AC XY: 43557 AN XY: 73772

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.623

Alfa AF: 0.640 Hom.: 38578

Bravo AF: 0.582

Asia WGS AF: 0.413 AC: 1440 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CEP170B-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.44
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2028414; hg19: chr14-105349388; COSMIC: COSV69024171;