chr6-167000051-T-C

Position:

• chr6-167000051-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000366847.9(CEP43):​c.103-9T>C variant causes a splice polypyrimidine tract, 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 ENST00000366847.9 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001090
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP43	NM_007045.4	c.103-9T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000366847.9	NP_008976.1
CEP43	NM_001278690.2	c.103-9T>C		splice_polypyrimidine_tract_variant, intron_variant			NP_001265619.1
CEP43	NM_194429.3	c.103-9T>C		splice_polypyrimidine_tract_variant, intron_variant			NP_919410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP43	ENST00000366847.9	c.103-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_007045.4	ENSP00000355812	P4

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

GnomAD3 exomes AF: 0.376 AC: 93630 AN: 249216 Hom.: 18949 AF XY: 0.381 AC XY: 51301 AN XY: 134824

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 SAS exome AF: 0.272

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

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.406

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

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.340

Alfa AF: 0.396 Hom.: 7529

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
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

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