Variant chr16-58543411-GA-G 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.4629delT(p.Leu1544fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,322,598 control chromosomes in the GnomAD database, including 8,091 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 4716 hom., cov: 21)

Exomes 𝑓: 0.25 ( 3375 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-GA-G is Benign according to our data. Variant chr16-58543411-GA-G is described in ClinVar as [Benign]. Clinvar id is 402549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-58543411-GA-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 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+195delT		intron_variant		ENST00000317147.10	NP_057368.3	A5YKK6-1
CNOT1	NM_206999.3 linkuse as main transcript	c.4629delT	p.Leu1544fs	frameshift_variant	31/31		NP_996882.1	A5YKK6-4
CNOT1	NM_001265612.2 linkuse as main transcript	c.4419+195delT		intron_variant			NP_001252541.1	A5YKK6-2
CNOT1	NR_049763.2 linkuse as main transcript	n.4692+195delT		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

36428

AN:

129714

Hom.:

4707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.276

GnomAD3 exomes

AF:

0.340

AC:

23153

AN:

68028

Hom.:

289

AF XY:

0.338

AC XY:

11916

AN XY:

35246

show subpopulations

Gnomad AFR exome

AF:

0.240

Gnomad AMR exome

AF:

0.383

Gnomad ASJ exome

AF:

0.331

Gnomad EAS exome

AF:

0.374

Gnomad SAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.328

Gnomad OTH exome

AF:

0.333

GnomAD4 exome

AF:

0.247

AC:

294644

AN:

1192822

Hom.:

3375

Cov.:

AF XY:

0.248

AC XY:

144263

AN XY:

582162

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.339

Gnomad4 ASJ exome

AF:

0.241

Gnomad4 EAS exome

AF:

0.308

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.279

Gnomad4 NFE exome

AF:

0.241

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.281

AC:

36455

AN:

129776

Hom.:

4716

Cov.:

AF XY:

0.289

AC XY:

18091

AN XY:

62542

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.381

Gnomad4 ASJ

AF:

0.270

Gnomad4 EAS

AF:

0.410

Gnomad4 SAS

AF:

0.367

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.279

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 19, 2021

- -

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