16-58553833-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_016284.5(CNOT1):c.2919G>A(p.Gln973Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,608,122 control chromosomes in the GnomAD database, including 90,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12973 hom., cov: 32)

Exomes 𝑓: 0.31 ( 77385 hom. )

Consequence

CNOT1
NM_016284.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.76

Publications

41 publications found

Variant links:

Genes affected

CNOT1 (HGNC:7877): (CCR4-NOT transcription complex subunit 1) Enables armadillo repeat domain binding activity; molecular adaptor activity; and nuclear receptor binding activity. Contributes to poly(A)-specific ribonuclease activity. Involved in several processes, including negative regulation of signal transduction; positive regulation of cytoplasmic mRNA processing body assembly; and regulation of gene expression. Located in P-body and cytosol. Part of CCR4-NOT complex. Implicated in holoprosencephaly. [provided by Alliance of Genome Resources, Apr 2022]

CNOT1 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
holoprosencephaly 12 with or without pancreatic agenesis
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
Vissers-Bodmer syndrome
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

CNOT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 16-58553833-C-T is Benign according to our data. Variant chr16-58553833-C-T is described in ClinVar as [Benign]. Clinvar id is 1217378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT1	NM_016284.5 link	c.2919G>A	p.Gln973Gln	synonymous_variant	Exon 22 of 49	ENST00000317147.10	NP_057368.3	A5YKK6-1
CNOT1	NM_001265612.2 link	c.2904G>A	p.Gln968Gln	synonymous_variant	Exon 22 of 49		NP_001252541.1	A5YKK6-2
CNOT1	NM_206999.3 link	c.2919G>A	p.Gln973Gln	synonymous_variant	Exon 22 of 31		NP_996882.1	A5YKK6-4
CNOT1	NR_049763.2 link	n.3177G>A		non_coding_transcript_exon_variant	Exon 22 of 50

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT1	ENST00000317147.10 link	c.2919G>A	p.Gln973Gln	synonymous_variant	Exon 22 of 49	1	NM_016284.5	ENSP00000320949.5		A5YKK6-1

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

59294

AN:

151958

Hom.:

12950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.573

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.384

GnomAD2 exomes

AF:

0.352

AC:

87032

AN:

246930

AF XY:

0.352

show subpopulations

Gnomad AFR exome

AF:

0.603

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.373

Gnomad EAS exome

AF:

0.565

Gnomad FIN exome

AF:

0.256

Gnomad NFE exome

AF:

0.297

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.314

AC:

457838

AN:

1456046

Hom.:

77385

Cov.:

AF XY:

0.317

AC XY:

229886

AN XY:

724252

show subpopulations

African (AFR)

AF:

0.606

AC:

20014

AN:

33028

American (AMR)

AF:

0.306

AC:

13450

AN:

44000

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

9781

AN:

25988

East Asian (EAS)

AF:

0.608

AC:

23805

AN:

39158

South Asian (SAS)

AF:

0.427

AC:

36386

AN:

85120

European-Finnish (FIN)

AF:

0.257

AC:

13620

AN:

52946

Middle Eastern (MID)

AF:

0.434

AC:

2495

AN:

5744

European-Non Finnish (NFE)

AF:

0.286

AC:

317763

AN:

1109904

Other (OTH)

AF:

0.341

AC:

20524

AN:

60158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

18789

37577

56366

75154

93943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.390

AC:

59361

AN:

152076

Hom.:

12973

Cov.:

AF XY:

0.391

AC XY:

29099

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.590

AC:

24462

AN:

41486

American (AMR)

AF:

0.322

AC:

4910

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

1315

AN:

3472

East Asian (EAS)

AF:

0.573

AC:

2960

AN:

5170

South Asian (SAS)

AF:

0.428

AC:

2064

AN:

4822

European-Finnish (FIN)

AF:

0.266

AC:

2811

AN:

10574

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.291

AC:

19754

AN:

67972

Other (OTH)

AF:

0.384

AC:

809

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1741

3483

5224

6966

8707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.340

Hom.:

21559

Bravo

AF:

0.403

Asia WGS

AF:

0.485

AC:

1686

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Vissers-Bodmer syndrome

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Holoprosencephaly 12 with or without pancreatic agenesis

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CNOT1-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.2

(source)

DANN

Benign

0.66

PhyloP100

1.8

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.010

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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16-58553833-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over