dbSNP rs10516143: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT6	NM_001370472.1 link	c.300-84T>A		intron_variant	Intron 3 of 11	ENST00000261951.9	NP_001357401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT6	ENST00000261951.9 link	c.300-84T>A		intron_variant	Intron 3 of 11	5	NM_001370472.1	ENSP00000261951.4		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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over