Genetic Variant CNOT6:c.300-84T>A (chr5-180553302-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001370472.1(CNOT6):c.300-84T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 864,250 control chromosomes in the GnomAD database, including 103,743 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 0.44 ( 15649 hom., cov: 31)

Exomes 𝑓: 0.49 ( 88094 hom. )

Consequence

CNOT6
NM_001370472.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.475

Publications

4 publications found

Variant links:

Genes affected

CNOT6 (HGNC:14099): (CCR4-NOT transcription complex subunit 6) This gene encodes the catalytic component of the CCR4-NOT core transcriptional regulation complex. The encoded protein has a 3'-5' RNase activity and prefers polyadenylated substrates. The CCR4-NOT complex plays a role in many cellular processes, including miRNA-mediated repression, mRNA degradation, and transcriptional regulation. [provided by RefSeq, Dec 2014]

CNOT6 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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370472.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNOT6	NM_001370472.1	MANE Select	c.300-84T>A	intron	N/A	NP_001357401.1	Q9ULM6
CNOT6	NM_001370473.1		c.300-84T>A	intron	N/A	NP_001357402.1
CNOT6	NM_001370474.1		c.15-84T>A	intron	N/A	NP_001357403.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNOT6	ENST00000261951.9	TSL:5 MANE Select	c.300-84T>A	intron	N/A	ENSP00000261951.4	Q9ULM6
CNOT6	ENST00000393356.7	TSL:1	c.300-84T>A	intron	N/A	ENSP00000377024.1	Q9ULM6
CNOT6	ENST00000618123.4	TSL:1	c.300-84T>A	intron	N/A	ENSP00000481893.1	Q9ULM6

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66669

AN:

151824

Hom.:

15648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.422

Gnomad ASJ

AF:

0.599

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.494

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.445

GnomAD4 exome

AF:

0.488

AC:

347476

AN:

712308

Hom.:

88094

AF XY:

0.490

AC XY:

184499

AN XY:

376554

show subpopulations

African (AFR)

AF:

0.285

AC:

5078

AN:

17810

American (AMR)

AF:

0.386

AC:

11292

AN:

29258

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

11255

AN:

18796

East Asian (EAS)

AF:

0.198

AC:

6871

AN:

34740

South Asian (SAS)

AF:

0.451

AC:

27633

AN:

61236

European-Finnish (FIN)

AF:

0.491

AC:

23710

AN:

48322

Middle Eastern (MID)

AF:

0.522

AC:

2155

AN:

4132

European-Non Finnish (NFE)

AF:

0.524

AC:

242714

AN:

463100

Other (OTH)

AF:

0.480

AC:

16768

AN:

34914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

7400

14800

22200

29600

37000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3820

7640

11460

15280

19100

<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:

0.439

AC:

66681

AN:

151942

Hom.:

15649

Cov.:

AF XY:

0.438

AC XY:

32545

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.286

AC:

11858

AN:

41444

American (AMR)

AF:

0.421

AC:

6435

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

2076

AN:

3464

East Asian (EAS)

AF:

0.231

AC:

1196

AN:

5172

South Asian (SAS)

AF:

0.433

AC:

2081

AN:

4808

European-Finnish (FIN)

AF:

0.494

AC:

5205

AN:

10528

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.536

AC:

36382

AN:

67934

Other (OTH)

AF:

0.439

AC:

927

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1771

3543

5314

7086

8857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.476

Hom.:

2127

Bravo

AF:

0.424

Asia WGS

AF:

0.296

AC:

1030

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.5

(source)

DANN

Benign

0.46

PhyloP100

0.47

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over