Variant 14-104883083-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001112726.3(CEP170B):c.626G>A(p.Arg209His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000683 in 1,565,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

CEP170B
NM_001112726.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.875

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034406602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP170B	NM_001112726.3 linkuse as main transcript	c.626G>A	p.Arg209His	missense_variant	8/19	ENST00000414716.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP170B	ENST00000414716.8 linkuse as main transcript	c.626G>A	p.Arg209His	missense_variant	8/19	1	NM_001112726.3	P1	Q9Y4F5-2
CEP170B	ENST00000556508.5 linkuse as main transcript	c.416G>A	p.Arg139His	missense_variant	7/18	5			Q9Y4F5-3

Frequencies

GnomAD3 genomes

AF:

0.0000858

AC:

AN:

151474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000971

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000867

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000884

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000133

AC:

AN:

180076

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

98980

show subpopulations

Gnomad AFR exome

AF:

0.000306

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00126

Gnomad EAS exome

AF:

0.0000723

Gnomad SAS exome

AF:

0.0000793

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000665

AC:

AN:

1414436

Hom.:

Cov.:

AF XY:

0.0000729

AC XY:

AN XY:

699676

show subpopulations

Gnomad4 AFR exome

AF:

0.0000921

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000868

Gnomad4 EAS exome

AF:

0.0000531

Gnomad4 SAS exome

AF:

0.000110

Gnomad4 FIN exome

AF:

0.0000236

Gnomad4 NFE exome

AF:

0.0000476

Gnomad4 OTH exome

AF:

0.0000681

GnomAD4 genome

AF:

0.0000858

AC:

AN:

151474

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

73938

show subpopulations

Gnomad4 AFR

AF:

0.0000971

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000867

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000884

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000226

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.0000764

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2024

The c.626G>A (p.R209H) alteration is located in exon 8 (coding exon 7) of the CEP170B gene. This alteration results from a G to A substitution at nucleotide position 626, causing the arginine (R) at amino acid position 209 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

.;.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

.;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.036

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.72

.;P;.

Vest4

0.28

MVP

0.23

MPC

0.28

ClinPred

0.016

GERP RS

2.2

gMVP

0.15

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