rs2301436

chr6-167024500-C-T

Variant summary

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

The NM_007045.4(CEP43):c.807-282C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,666 control chromosomes in the GnomAD database, including 13,645 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 0.42 (13645 hom., cov: 31)
• Consequence: CEP43 NM_007045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP43	NM_007045.4	c.807-282C>T		intron_variant		ENST00000366847.9
CEP43	NM_001278690.2	c.666-282C>T		intron_variant
CEP43	NM_194429.3	c.747-282C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP43	ENST00000366847.9	c.807-282C>T		intron_variant		1	NM_007045.4	P4

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63839 AN: 151548 Hom.: 13646 Cov.: 31

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.421 AC: 63860 AN: 151666 Hom.: 13645 Cov.: 31 AF XY: 0.417 AC XY: 30862 AN XY: 74094

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.395

Alfa AF: 0.461 Hom.: 35595

Bravo AF: 0.412

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.27
Dann	Benign	0.51

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: rs2301436; hg19: chr6-167437988;