Genetic Variant CNOT9:c.-289A>C (chr2-218568666-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.211

Publications

3 publications found

Variant links:

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]

CNOT9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	MANE	Protein	UniProt
CNOT9	NM_005444.3 link	c.-289A>C	upstream_gene_variant	ENST00000273064.11	NP_005435.1	Q92600-1D5MQE1
CNOT9	NM_001271634.2 link	c.-289A>C	upstream_gene_variant		NP_001258563.1	Q92600-2
CNOT9	NM_001271635.2 link	c.-289A>C	upstream_gene_variant		NP_001258564.1	Q92600-3
CNOT9	NR_073390.2 link	n.-173A>C	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT9	ENST00000273064.11 link	c.-289A>C		upstream_gene_variant		1	NM_005444.3	ENSP00000273064.6		Q92600-1

Frequencies

GnomAD3 genomes

AF:

0.0568

AC:

8635

AN:

152102

Hom.:

364

Cov.:

show subpopulations

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.:

AF XY:

0.0410

AC XY:

5590

AN XY:

136406

show subpopulations

African (AFR)

AF:

0.107

AC:

760

AN:

7132

American (AMR)

AF:

0.0246

AC:

180

AN:

7328

Ashkenazi Jewish (ASJ)

AF:

0.0289

AC:

269

AN:

9308

East Asian (EAS)

AF:

0.109

AC:

2378

AN:

21786

South Asian (SAS)

AF:

0.0432

AC:

583

AN:

13490

European-Finnish (FIN)

AF:

0.0307

AC:

659

AN:

21484

Middle Eastern (MID)

AF:

0.0331

AC:

AN:

1298

European-Non Finnish (NFE)

AF:

0.0323

AC:

5296

AN:

164096

Other (OTH)

AF:

0.0417

AC:

697

AN:

16730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

473

946

1418

1891

2364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0568

AC:

8649

AN:

152220

Hom.:

365

Cov.:

AF XY:

0.0555

AC XY:

4132

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.110

AC:

4585

AN:

41514

American (AMR)

AF:

0.0277

AC:

424

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0317

AC:

110

AN:

3470

East Asian (EAS)

AF:

0.118

AC:

610

AN:

5180

South Asian (SAS)

AF:

0.0447

AC:

216

AN:

4832

European-Finnish (FIN)

AF:

0.0273

AC:

289

AN:

10604

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0336

AC:

2283

AN:

68002

Other (OTH)

AF:

0.0469

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

419

838

1256

1675

2094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0464

Hom.:

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

(source)

DANN

Benign

0.43

PhyloP100

0.21

PromoterAI

0.029

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over