6-167021198-T-C

Variant names:

• chr6-167021198-T-C
• rs1894603
• NM_007045.4:c.580-1211T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007045.4(CEP43):​c.580-1211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,070 control chromosomes in the GnomAD database, including 13,666 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 (13666 hom., cov: 32)
• Consequence: CEP43 NM_007045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007045.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP43	NM_007045.4	MANE Select	c.580-1211T>C		intron	N/A	NP_008976.1
	CEP43	NM_194429.3		c.520-1211T>C		intron	N/A	NP_919410.1
	CEP43	NM_001278690.2		c.439-1211T>C		intron	N/A	NP_001265619.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP43	ENST00000366847.9	TSL:1 MANE Select	c.580-1211T>C		intron	N/A	ENSP00000355812.3
	ENSG00000272980	ENST00000705249.1		c.520-1211T>C		intron	N/A	ENSP00000516101.1
	CEP43	ENST00000349556.5	TSL:1	c.520-1211T>C		intron	N/A	ENSP00000230248.6

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63860 AN: 151950 Hom.: 13666 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.420 AC: 63883 AN: 152070 Hom.: 13666 Cov.: 32 AF XY: 0.415 AC XY: 30852 AN XY: 74326

African (AFR) AF: 0.376 AC: 15579 AN: 41454

American (AMR) AF: 0.361 AC: 5522 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1500 AN: 3470

East Asian (EAS) AF: 0.377 AC: 1950 AN: 5176

South Asian (SAS) AF: 0.317 AC: 1527 AN: 4824

European-Finnish (FIN) AF: 0.415 AC: 4378 AN: 10550

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

European-Non Finnish (NFE) AF: 0.473 AC: 32189 AN: 67992

Other (OTH) AF: 0.395 AC: 832 AN: 2108

Alfa AF: 0.456 Hom.: 7985

Bravo AF: 0.412

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0060
DANN	Benign	0.35
PhyloP100		-1.6
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: rs1894603; hg19: chr6-167434686;