rs151606

chr6-167016994-T-Achr6-167016994-T-Cchr6-167016994-T-G

Variant summary

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

The NM_007045.4(CEP43):c.579+3427T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 149,316 control chromosomes in the GnomAD database, including 49,138 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 0.81 (49138 hom., cov: 28)
• Consequence: CEP43 NM_007045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.964

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP43	NM_007045.4	c.579+3427T>A		intron_variant		ENST00000366847.9
CEP43	NM_001278690.2	c.439-5415T>A		intron_variant
CEP43	NM_194429.3	c.520-5415T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP43	ENST00000366847.9	c.579+3427T>A		intron_variant		1	NM_007045.4	P4

Frequencies

GnomAD3 genomes AF: 0.811 AC: 121074 AN: 149218 Hom.: 49102 Cov.: 28

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.811 AC: 121155 AN: 149316 Hom.: 49138 Cov.: 28 AF XY: 0.812 AC XY: 59259 AN XY: 72980

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.824

Alfa AF: 0.811 Hom.: 4996

Asia WGS AF: 0.889 AC: 3047 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.34
Dann	Benign	0.18

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: rs151606; hg19: chr6-167430482;