6-167024415-A-G

Variant names:

• chr6-167024415-A-G
• rs16899799
• NM_007045.4:c.807-367A>G

Variant summary

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

The ENST00000366847.9(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 ENST00000366847.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0841 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366847.9. 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.807-367A>G		intron	N/A	NP_008976.1
	CEP43	NM_194429.3		c.747-367A>G		intron	N/A	NP_919410.1
	CEP43	NM_001278690.2		c.666-367A>G		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.807-367A>G		intron	N/A	ENSP00000355812.3
	ENSG00000272980	ENST00000705249.1		c.747-367A>G		intron	N/A	ENSP00000516101.1
	CEP43	ENST00000349556.5	TSL:1	c.747-367A>G		intron	N/A	ENSP00000230248.6

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

African (AFR) AF: 0.0244 AC: 1013 AN: 41556

American (AMR) AF: 0.0149 AC: 228 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3470

East Asian (EAS) AF: 0.0909 AC: 470 AN: 5172

South Asian (SAS) AF: 0.0374 AC: 180 AN: 4818

European-Finnish (FIN) AF: 0.00490 AC: 52 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1027 AN: 68022

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0174 Hom.: 4

Bravo AF: 0.0218

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.32
PhyloP100		-0.43
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: rs16899799; hg19: chr6-167437903;