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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PVS1_ModerateBP6_ModerateBS1BS2

The NM_206999.3(CNOT1):c.4628_4629delTT(p.Phe1543fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.000658 in 1,346,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 21)

Exomes 𝑓: 0.00068 ( 0 hom. )

Consequence

CNOT1
NM_206999.3 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.77

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 -8 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 0.00601 CDS is truncated, and there are 2 pathogenic variants in the truncated region.

BP6

Variant 16-58543411-GAA-G is Benign according to our data. Variant chr16-58543411-GAA-G is described in ClinVar as [Benign]. Clinvar id is 2646576.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00047 (61/129878) while in subpopulation EAS AF= 0.000863 (4/4634). AF 95% confidence interval is 0.000388. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High AC in GnomAd4 at 61 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNOT1	NM_016284.5 linkuse as main transcript	c.4434+194_4434+195delTT		intron_variant		ENST00000317147.10	NP_057368.3	A5YKK6-1
CNOT1	NM_206999.3 linkuse as main transcript	c.4628_4629delTT	p.Phe1543fs	frameshift_variant	31/31		NP_996882.1	A5YKK6-4
CNOT1	NM_001265612.2 linkuse as main transcript	c.4419+194_4419+195delTT		intron_variant			NP_001252541.1	A5YKK6-2
CNOT1	NR_049763.2 linkuse as main transcript	n.4692+194_4692+195delTT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNOT1	ENST00000317147.10 linkuse as main transcript	c.4434+194_4434+195delTT		intron_variant		1	NM_016284.5	ENSP00000320949.5		A5YKK6-1

Frequencies

GnomAD3 genomes

AF:

0.000462

AC:

AN:

129812

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000859

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00136

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000533

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00345

AC:

235

AN:

68028

Hom.:

AF XY:

0.00386

AC XY:

136

AN XY:

35246

show subpopulations

Gnomad AFR exome

AF:

0.000875

Gnomad AMR exome

AF:

0.00485

Gnomad ASJ exome

AF:

0.00426

Gnomad EAS exome

AF:

0.00208

Gnomad SAS exome

AF:

0.00415

Gnomad FIN exome

AF:

0.00241

Gnomad NFE exome

AF:

0.00378

Gnomad OTH exome

AF:

0.00363

GnomAD4 exome

AF:

0.000678

AC:

825

AN:

1216198

Hom.:

AF XY:

0.000713

AC XY:

423

AN XY:

593526

show subpopulations

Gnomad4 AFR exome

AF:

0.000310

Gnomad4 AMR exome

AF:

0.00229

Gnomad4 ASJ exome

AF:

0.000621

Gnomad4 EAS exome

AF:

0.000848

Gnomad4 SAS exome

AF:

0.00159

Gnomad4 FIN exome

AF:

0.00135

Gnomad4 NFE exome

AF:

0.000573

Gnomad4 OTH exome

AF:

0.000537

GnomAD4 genome

AF:

0.000470

AC:

AN:

129878

Hom.:

Cov.:

AF XY:

0.000543

AC XY:

AN XY:

62592

show subpopulations

Gnomad4 AFR

AF:

0.000263

Gnomad4 AMR

AF:

0.000446

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000863

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00136

Gnomad4 NFE

AF:

0.000533

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

CNOT1: BS1, BS2 -

CNOT1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 28, 2020

This variant is classified as likely 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

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