rs162295

Variant names:

• chr6-167040609-A-C
• rs162295
• NM_007045.4:c.*631A>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.*631A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,038,892 control chromosomes in the GnomAD database, including 45,584 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 0.28 (6844 hom., cov: 33)
  • Exomes 𝑓: 0.29 (38740 hom.)
• Consequence: CEP43 NM_007045.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 17 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP43	NM_007045.4	c.*631A>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000366847.9	NP_008976.1
CEP43	NM_194429.3	c.*631A>C		3_prime_UTR_variant	Exon 12 of 12		NP_919410.1
CEP43	NM_001278690.2	c.*490A>C		3_prime_UTR_variant	Exon 11 of 11		NP_001265619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP43	ENST00000366847.9	c.*631A>C		3_prime_UTR_variant	Exon 13 of 13	1	NM_007045.4	ENSP00000355812.3
ENSG00000272980	ENST00000705249.1	c.1065+6638A>C		intron_variant	Intron 11 of 12			ENSP00000516101.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42480 AN: 152052 Hom.: 6842 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.292 AC: 258602 AN: 886722 Hom.: 38740 Cov.: 20 AF XY: 0.293 AC XY: 120191 AN XY: 410486

African (AFR) AF: 0.115 AC: 2080 AN: 18064

American (AMR) AF: 0.494 AC: 2205 AN: 4462

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 2999 AN: 8478

East Asian (EAS) AF: 0.397 AC: 4771 AN: 12032

South Asian (SAS) AF: 0.414 AC: 7501 AN: 18128

European-Finnish (FIN) AF: 0.287 AC: 136 AN: 474

Middle Eastern (MID) AF: 0.336 AC: 651 AN: 1940

European-Non Finnish (NFE) AF: 0.288 AC: 228228 AN: 791410

Other (OTH) AF: 0.316 AC: 10031 AN: 31734

GnomAD4 genome AF: 0.279 AC: 42493 AN: 152170 Hom.: 6844 Cov.: 33 AF XY: 0.286 AC XY: 21255 AN XY: 74376

African (AFR) AF: 0.134 AC: 5555 AN: 41536

American (AMR) AF: 0.430 AC: 6570 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1189 AN: 3466

East Asian (EAS) AF: 0.418 AC: 2159 AN: 5170

South Asian (SAS) AF: 0.412 AC: 1989 AN: 4824

European-Finnish (FIN) AF: 0.326 AC: 3449 AN: 10578

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20352 AN: 68004

Other (OTH) AF: 0.325 AC: 686 AN: 2110

Alfa AF: 0.303 Hom.: 4156

Bravo AF: 0.285

Asia WGS AF: 0.390 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.61
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs162295; hg19: chr6-167454097; COSMIC: COSV62761649; COSMIC: COSV62761649;