rs37060

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016284.5(CNOT1):c.5896-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,610,182 control chromosomes in the GnomAD database, including 56,368 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4896 hom., cov: 33)

Exomes 𝑓: 0.26 ( 51472 hom. )

Consequence

CNOT1
NM_016284.5 splice_region, intron

Scores

Splicing: ADA: 0.000008593

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.590

Publications

40 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-58532400-G-A is Benign according to our data. Variant chr16-58532400-G-A is described in ClinVar as Benign. ClinVar VariationId is 1217372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CNOT1	NM_016284.5 link	c.5896-5C>T	splice_region_variant, intron_variant	Intron 40 of 48	ENST00000317147.10	NP_057368.3	A5YKK6-1
CNOT1	NM_001265612.2 link	c.5881-5C>T	splice_region_variant, intron_variant	Intron 40 of 48		NP_001252541.1	A5YKK6-2
CNOT1	NR_049763.2 link	n.6154-5C>T	splice_region_variant, intron_variant	Intron 40 of 49

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT1	ENST00000317147.10 link	c.5896-5C>T		splice_region_variant, intron_variant	Intron 40 of 48	1	NM_016284.5	ENSP00000320949.5		A5YKK6-1

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36906

AN:

151982

Hom.:

4881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.231

GnomAD2 exomes

AF:

0.291

AC:

72945

AN:

250324

AF XY:

0.286

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.452

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.260

AC:

379032

AN:

1458080

Hom.:

51472

Cov.:

AF XY:

0.261

AC XY:

189096

AN XY:

724590

show subpopulations

African (AFR)

AF:

0.148

AC:

4934

AN:

33396

American (AMR)

AF:

0.438

AC:

19531

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

6717

AN:

26086

East Asian (EAS)

AF:

0.354

AC:

13993

AN:

39544

South Asian (SAS)

AF:

0.319

AC:

27476

AN:

86142

European-Finnish (FIN)

AF:

0.266

AC:

14153

AN:

53288

Middle Eastern (MID)

AF:

0.207

AC:

1189

AN:

5742

European-Non Finnish (NFE)

AF:

0.248

AC:

275166

AN:

1109036

Other (OTH)

AF:

0.263

AC:

15873

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

15676

31352

47029

62705

78381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9476

18952

28428

37904

47380

<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:

0.243

AC:

36948

AN:

152102

Hom.:

4896

Cov.:

AF XY:

0.247

AC XY:

18368

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.158

AC:

6565

AN:

41486

American (AMR)

AF:

0.349

AC:

5336

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

893

AN:

3468

East Asian (EAS)

AF:

0.381

AC:

1968

AN:

5162

South Asian (SAS)

AF:

0.336

AC:

1619

AN:

4822

European-Finnish (FIN)

AF:

0.257

AC:

2711

AN:

10564

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.251

AC:

17098

AN:

68004

Other (OTH)

AF:

0.235

AC:

496

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1415

2830

4244

5659

7074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.253

Hom.:

11466

Bravo

AF:

0.245

Asia WGS

AF:

0.353

AC:

1229

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

May 04, 2021

GeneDx

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

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.4

(source)

DANN

Benign

0.43

PhyloP100

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000086

dbscSNV1_RF

Benign

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over