rs6734184

chr2-218568666-A-C

Variant summary

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

The ENST00000627282.2(CNOT9):c.-289A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 414,872 control chromosomes in the GnomAD database, including 676 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 0.057 (365 hom., cov: 33)
  • Exomes 𝑓: 0.041 (311 hom.)
• Consequence: CNOT9 ENST00000627282.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

Genes affected

CNOT9 (HGNC:10445): (CCR4-NOT transcription complex subunit 9) This gene encodes a member of the highly conserved RCD1 protein family. The encoded protein is a transcriptional cofactor and a core protein of the CCR4-NOT complex. It may be involved in signal transduction as well as retinoic acid-regulated cell differentiation and development. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNOT9	ENST00000627282.2	c.-289A>C		5_prime_UTR_variant	1/9	2

Frequencies

GnomAD3 genomes AF: 0.0568 AC: 8635 AN: 152102 Hom.: 364 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0474

GnomAD4 exome AF: 0.0414 AC: 10865 AN: 262652 Hom.: 311 Cov.: 0 AF XY: 0.0410 AC XY: 5590 AN XY: 136406

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0246

Gnomad4 ASJ exome AF: 0.0289

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.0432

Gnomad4 FIN exome AF: 0.0307

Gnomad4 NFE exome AF: 0.0323

Gnomad4 OTH exome AF: 0.0417

GnomAD4 genome AF: 0.0568 AC: 8649 AN: 152220 Hom.: 365 Cov.: 33 AF XY: 0.0555 AC XY: 4132 AN XY: 74438

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0277

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0447

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0336

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0464 Hom.: 33

Bravo AF: 0.0599

Asia WGS AF: 0.0730 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	7.2
Dann	Benign	0.43

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: rs6734184; hg19: chr2-219433389; COSMIC: COSV51445726; COSMIC: COSV51445726;