rs162295

chr6-167040609-A-C

Variant summary

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

The NM_007045.4(CEP43):c.*631A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,038,892 control chromosomes in the GnomAD database, including 45,584 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 0.28 (6844 hom., cov: 33)
  • Exomes 𝑓: 0.29 (38740 hom.)
• Consequence: CEP43 NM_007045.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP43	NM_007045.4	c.*631A>C		3_prime_UTR_variant	13/13	ENST00000366847.9
CEP43	NM_001278690.2	c.*490A>C		3_prime_UTR_variant	11/11
CEP43	NM_194429.3	c.*631A>C		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP43	ENST00000366847.9	c.*631A>C		3_prime_UTR_variant	13/13	1	NM_007045.4	P4

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42480 AN: 152052 Hom.: 6842 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.292 AC: 258602 AN: 886722 Hom.: 38740 Cov.: 20 AF XY: 0.293 AC XY: 120191 AN XY: 410486

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.279 AC: 42493 AN: 152170 Hom.: 6844 Cov.: 33 AF XY: 0.286 AC XY: 21255 AN XY: 74376

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.325

Alfa AF: 0.306 Hom.: 3797

Bravo AF: 0.285

Asia WGS AF: 0.390 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.5
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs162295; hg19: chr6-167454097; COSMIC: COSV62761649; COSMIC: COSV62761649;