rs16899799

chr6-167024415-A-G

Variant summary

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

The NM_007045.4(CEP43):c.807-367A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 152,284 control chromosomes in the GnomAD database, including 50 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 0.020 (50 hom., cov: 32)
• Consequence: CEP43 NM_007045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP43	NM_007045.4	c.807-367A>G		intron_variant		ENST00000366847.9
CEP43	NM_001278690.2	c.666-367A>G		intron_variant
CEP43	NM_194429.3	c.747-367A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP43	ENST00000366847.9	c.807-367A>G		intron_variant		1	NM_007045.4	P4

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3071 AN: 152168 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.0909

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0220

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

GnomAD4 genome AF: 0.0202 AC: 3081 AN: 152284 Hom.: 50 Cov.: 32 AF XY: 0.0207 AC XY: 1538 AN XY: 74460

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.0149

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.0909

Gnomad4 SAS AF: 0.0374

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0168 Hom.: 4

Bravo AF: 0.0218

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.30
Dann	Benign	0.32

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: rs16899799; hg19: chr6-167437903;