Genetic Variant ENST00000627282.2: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:

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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

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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