rs7749278

chr6-167021837-T-C

Variant summary

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

The NM_007045.4(CEP43):c.580-572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,046 control chromosomes in the GnomAD database, including 13,931 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 0.43 (13931 hom., cov: 32)
• Consequence: CEP43 NM_007045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94

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=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP43	NM_007045.4	c.580-572T>C		intron_variant		ENST00000366847.9
CEP43	NM_001278690.2	c.439-572T>C		intron_variant
CEP43	NM_194429.3	c.520-572T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP43	ENST00000366847.9	c.580-572T>C		intron_variant		1	NM_007045.4	P4

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64602 AN: 151928 Hom.: 13933 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.425 AC: 64625 AN: 152046 Hom.: 13931 Cov.: 32 AF XY: 0.421 AC XY: 31272 AN XY: 74334

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.399

Alfa AF: 0.459 Hom.: 15678

Bravo AF: 0.417

Asia WGS AF: 0.399 AC: 1387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.012
Dann	Benign	0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7749278; hg19: chr6-167435325;