Variant chr14-104880392-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001112726.3(CEP170B):c.439A>C(p.Arg147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,612,588 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 15 hom. )

Consequence

CEP170B
NM_001112726.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.50

Variant links:

Genes affected

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

CEP170B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 14-104880392-A-C is Benign according to our data. Variant chr14-104880392-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 787955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.5 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00543 (826/152178) while in subpopulation AFR AF= 0.0182 (755/41496). AF 95% confidence interval is 0.0171. There are 9 homozygotes in gnomad4. There are 382 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP170B	NM_001112726.3 linkuse as main transcript	c.439A>C	p.Arg147=	synonymous_variant	6/19	ENST00000414716.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP170B	ENST00000414716.8 linkuse as main transcript	c.439A>C	p.Arg147=	synonymous_variant	6/19	1	NM_001112726.3	P1	Q9Y4F5-2
CEP170B	ENST00000556508.5 linkuse as main transcript	c.229A>C	p.Arg77=	synonymous_variant	5/18	5			Q9Y4F5-3

Frequencies

GnomAD3 genomes

AF:

0.00541

AC:

823

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00142

AC:

352

AN:

247046

Hom.:

AF XY:

0.00123

AC XY:

166

AN XY:

134566

show subpopulations

Gnomad AFR exome

AF:

0.0174

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000984

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000260

Gnomad OTH exome

AF:

0.00217

GnomAD4 exome

AF:

0.000808

AC:

1180

AN:

1460410

Hom.:

Cov.:

AF XY:

0.000772

AC XY:

561

AN XY:

726466

show subpopulations

Gnomad4 AFR exome

AF:

0.0225

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00543

AC:

826

AN:

152178

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

382

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0182

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00648

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000297

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 03, 2017

- -

CEP170B-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 2019

This variant is classified as likely 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

-0.51

CADD

Benign

7.7

DANN

Benign

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over