Variant chr6-167024804-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007045.4(CEP43):c.829G>C(p.Ala277Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,613,524 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 88 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 94 hom. )

Consequence

CEP43
NM_007045.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.721

Variant links:

Genes affected

CEP43 (HGNC:17012): (centrosomal protein 43) This gene encodes a largely hydrophilic centrosomal protein that is required for anchoring microtubules to subcellular structures. A t(6;8)(q27;p11) chromosomal translocation, fusing this gene and the fibroblast growth factor receptor 1 (FGFR1) gene, has been found in cases of myeloproliferative disorder. The resulting chimeric protein contains the N-terminal leucine-rich region of this encoded protein fused to the catalytic domain of FGFR1. Alterations in this gene may also be associated with Crohn's disease, Graves' disease, and vitiligo. Alternatively spliced transcript variants that encode different proteins have been identified. [provided by RefSeq, Jul 2013]

CEP43 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019060969).

BP6

Variant 6-167024804-G-C is Benign according to our data. Variant chr6-167024804-G-C is described in ClinVar as [Benign]. Clinvar id is 786767.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CEP43	NM_007045.4 linkuse as main transcript	c.829G>C	p.Ala277Pro	missense_variant	9/13	ENST00000366847.9
CEP43	NM_194429.3 linkuse as main transcript	c.769G>C	p.Ala257Pro	missense_variant	8/12
CEP43	NM_001278690.2 linkuse as main transcript	c.688G>C	p.Ala230Pro	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP43	ENST00000366847.9 linkuse as main transcript	c.829G>C	p.Ala277Pro	missense_variant	9/13	1	NM_007045.4	P4	O95684-1

Frequencies

GnomAD3 genomes

AF:

0.0201

AC:

3055

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0675

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.00793

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.00543

AC:

1362

AN:

250984

Hom.:

AF XY:

0.00404

AC XY:

548

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.0723

Gnomad AMR exome

AF:

0.00363

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00222

AC:

3238

AN:

1461300

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

1400

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.0735

Gnomad4 AMR exome

AF:

0.00401

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000279

Gnomad4 OTH exome

AF:

0.00447

GnomAD4 genome

AF:

0.0200

AC:

3050

AN:

152224

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1464

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0672

Gnomad4 AMR

AF:

0.00785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.0228

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0649

AC:

286

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00648

AC:

787

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000475

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.2

DANN

Benign

0.45

DEOGEN2

Benign

0.061

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.54

T;T;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

L;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.37

N;.;N

REVEL

Benign

0.059

Sift

Benign

0.26

T;.;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.076

MVP

0.17

MPC

0.054

ClinPred

0.012

GERP RS

2.5

Varity_R

0.053

gMVP

0.095

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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