NM_007045.4:c.103-9T>C

Variant names:

• chr6-167000051-T-C
• rs12212247
• NM_007045.4:c.103-9T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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

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]

ENSG00000272980 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007045.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP43	NM_007045.4	MANE Select	c.103-9T>C		intron	N/A	NP_008976.1
	CEP43	NM_194429.3		c.103-9T>C		intron	N/A	NP_919410.1
	CEP43	NM_001278690.2		c.103-9T>C		intron	N/A	NP_001265619.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP43	ENST00000366847.9	TSL:1 MANE Select	c.103-9T>C		intron	N/A	ENSP00000355812.3
	ENSG00000272980	ENST00000705249.1		c.103-9T>C		intron	N/A	ENSP00000516101.1
	CEP43	ENST00000349556.5	TSL:1	c.103-9T>C		intron	N/A	ENSP00000230248.6

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53015 AN: 152016 Hom.: 10447 Cov.: 33

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

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.: 29 AF XY: 0.424 AC XY: 306246 AN XY: 721434

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

GnomAD4 genome AF: 0.348 AC: 53013 AN: 152138 Hom.: 10448 Cov.: 33 AF XY: 0.345 AC XY: 25635 AN XY: 74372

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
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)

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

Other links and lift over

dbSNP: rs12212247; hg19: chr6-167413539; COSMIC: COSV62760892; COSMIC: COSV62760892;