6-167024500-C-T

Variant names:

• chr6-167024500-C-T
• rs2301436
• NM_007045.4:c.807-282C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 88 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=-0.94).
• 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 rank	MANE	Protein	UniProt
CEP43	NM_007045.4	c.807-282C>T		intron_variant	Intron 8 of 12	ENST00000366847.9	NP_008976.1
CEP43	NM_194429.3	c.747-282C>T		intron_variant	Intron 7 of 11		NP_919410.1
CEP43	NM_001278690.2	c.666-282C>T		intron_variant	Intron 6 of 10		NP_001265619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP43	ENST00000366847.9	c.807-282C>T		intron_variant	Intron 8 of 12	1	NM_007045.4	ENSP00000355812.3
ENSG00000272980	ENST00000705249.1	c.747-282C>T		intron_variant	Intron 7 of 12			ENSP00000516101.1

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

African (AFR) AF: 0.377 AC: 15568 AN: 41314

American (AMR) AF: 0.362 AC: 5520 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1501 AN: 3472

East Asian (EAS) AF: 0.377 AC: 1938 AN: 5142

South Asian (SAS) AF: 0.330 AC: 1582 AN: 4800

European-Finnish (FIN) AF: 0.415 AC: 4348 AN: 10470

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32166 AN: 67900

Other (OTH) AF: 0.395 AC: 833 AN: 2108

Alfa AF: 0.456 Hom.: 66822

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
PhyloP100		-0.078
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2301436; hg19: chr6-167437988;