Variant 16-58543411-GAAA-GAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The NM_206999.3(CNOT1):c.4629dupT(p.Leu1544fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,089,636 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 21)

Exomes 𝑓: 0.16 ( 0 hom. )

Consequence

CNOT1
NM_206999.3 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0160

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 links:

CNOT1 (HGNC:):

CNOT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0058 CDS is truncated, and there are 2 pathogenic variants in the truncated region.

BP6

Variant 16-58543411-G-GA is Benign according to our data. Variant chr16-58543411-G-GA is described in ClinVar as [Benign]. Clinvar id is 587551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNOT1	NM_016284.5 linkuse as main transcript	c.4434+195dupT		intron_variant		ENST00000317147.10	NP_057368.3	A5YKK6-1
CNOT1	NM_206999.3 linkuse as main transcript	c.4629dupT	p.Leu1544fs	frameshift_variant	31/31		NP_996882.1	A5YKK6-4
CNOT1	NM_001265612.2 linkuse as main transcript	c.4419+195dupT		intron_variant			NP_001252541.1	A5YKK6-2
CNOT1	NR_049763.2 linkuse as main transcript	n.4692+195dupT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNOT1	ENST00000317147.10 linkuse as main transcript	c.4434+195dupT		intron_variant		1	NM_016284.5	ENSP00000320949.5		A5YKK6-1

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

405

AN:

129714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00542

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00358

Gnomad ASJ

AF:

0.00126

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00139

Gnomad FIN

AF:

0.00177

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00214

Gnomad OTH

AF:

0.00691

GnomAD3 exomes

AF:

0.148

AC:

10061

AN:

68028

Hom.:

AF XY:

0.150

AC XY:

5281

AN XY:

35246

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.124

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.159

AC:

152156

AN:

959856

Hom.:

Cov.:

AF XY:

0.159

AC XY:

74431

AN XY:

469534

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.142

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.162

Gnomad4 OTH exome

AF:

0.157

GnomAD4 genome

AF:

0.00316

AC:

410

AN:

129780

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

219

AN XY:

62528

show subpopulations

Gnomad4 AFR

AF:

0.00552

Gnomad4 AMR

AF:

0.00357

Gnomad4 ASJ

AF:

0.00126

Gnomad4 EAS

AF:

0.00194

Gnomad4 SAS

AF:

0.00116

Gnomad4 FIN

AF:

0.00177

Gnomad4 NFE

AF:

0.00214

Gnomad4 OTH

AF:

0.00797

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genomic Research Center, Shahid Beheshti University of Medical Sciences	Aug 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over