Genetic Variant CEP43:c.103-9T>C (chr6-167000051-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007045.4(CEP43):c.103-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,601,016 control chromosomes in the GnomAD database, including 147,506 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 10448 hom., cov: 33)

Exomes 𝑓: 0.43 ( 137058 hom. )

Consequence

CEP43
NM_007045.4 intron

Scores

Splicing: ADA: 0.0001090

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.229

Publications

21 publications found

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:

ENSG00000272980 (HGNC:):

ENSG00000272980 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CEP43	NM_007045.4 link	c.103-9T>C	intron_variant	Intron 1 of 12	ENST00000366847.9	NP_008976.1
CEP43	NM_194429.3 link	c.103-9T>C	intron_variant	Intron 1 of 11		NP_919410.1
CEP43	NM_001278690.2 link	c.103-9T>C	intron_variant	Intron 1 of 10		NP_001265619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP43	ENST00000366847.9 link	c.103-9T>C		intron_variant	Intron 1 of 12	1	NM_007045.4	ENSP00000355812.3
ENSG00000272980	ENST00000705249.1 link	c.103-9T>C		intron_variant	Intron 1 of 12			ENSP00000516101.1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53015

AN:

152016

Hom.:

10447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.458

Gnomad OTH

AF:

0.344

GnomAD2 exomes

AF:

0.376

AC:

93630

AN:

249216

AF XY:

0.381

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.277

Gnomad ASJ exome

AF:

0.457

Gnomad EAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.405

Gnomad NFE exome

AF:

0.465

Gnomad OTH exome

AF:

0.399

GnomAD4 exome

AF:

0.427

AC:

618897

AN:

1448878

Hom.:

137058

Cov.:

AF XY:

0.424

AC XY:

306246

AN XY:

721434

show subpopulations

African (AFR)

AF:

0.162

AC:

5380

AN:

33180

American (AMR)

AF:

0.282

AC:

12473

AN:

44290

Ashkenazi Jewish (ASJ)

AF:

0.452

AC:

11761

AN:

26032

East Asian (EAS)

AF:

0.321

AC:

12688

AN:

39516

South Asian (SAS)

AF:

0.278

AC:

23799

AN:

85658

European-Finnish (FIN)

AF:

0.413

AC:

22001

AN:

53238

Middle Eastern (MID)

AF:

0.434

AC:

2483

AN:

5722

European-Non Finnish (NFE)

AF:

0.458

AC:

503953

AN:

1101260

Other (OTH)

AF:

0.406

AC:

24359

AN:

59982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

13967

27934

41901

55868

69835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14638

29276

43914

58552

73190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.348

AC:

53013

AN:

152138

Hom.:

10448

Cov.:

AF XY:

0.345

AC XY:

25635

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.172

AC:

7136

AN:

41516

American (AMR)

AF:

0.330

AC:

5039

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.449

AC:

1558

AN:

3470

East Asian (EAS)

AF:

0.285

AC:

1474

AN:

5172

South Asian (SAS)

AF:

0.271

AC:

1309

AN:

4828

European-Finnish (FIN)

AF:

0.409

AC:

4317

AN:

10564

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.458

AC:

31153

AN:

67994

Other (OTH)

AF:

0.340

AC:

717

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1706

3412

5117

6823

8529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

516

1032

1548

2064

2580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.402

Hom.:

10614

Bravo

AF:

0.333

Asia WGS

AF:

0.263

AC:

917

AN:

3478

EpiCase

AF:

0.455

EpiControl

AF:

0.457

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.5

(source)

DANN

Benign

0.68

PhyloP100

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.024

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over