chr16-58523438-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_016284.5(CNOT1):c.6849C>T(p.Tyr2283Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.0396 in 1,613,818 control chromosomes in the GnomAD database, including 1,456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 84 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1372 hom. )

Consequence

CNOT1
NM_016284.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.75

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:

SETD6 (HGNC:26116): (SET domain containing 6, protein lysine methyltransferase) This gene encodes a methyltransferase that adds a methyl group to the histone H2AZ, which is involved in nuclear receptor-dependent transcription. The protein also interacts with several endogenous proteins which are involved in nuclear hormone receptor signaling. A related pseudogene is located on chromosome 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

SETD6 links:

ENSG00000276259 (HGNC:):

ENSG00000276259 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 16-58523438-G-A is Benign according to our data. Variant chr16-58523438-G-A is described in ClinVar as [Benign]. Clinvar id is 1569231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0296 (4510/152286) while in subpopulation NFE AF= 0.0482 (3276/68004). AF 95% confidence interval is 0.0468. There are 84 homozygotes in gnomad4. There are 2086 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4510 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT1	NM_016284.5 link	c.6849C>T	p.Tyr2283Tyr	synonymous_variant	Exon 47 of 49	ENST00000317147.10	NP_057368.3	A5YKK6-1
SETD6	NM_001160305.4 link	c.*4409G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000219315.9	NP_001153777.1	Q8TBK2-1
CNOT1	NM_001265612.2 link	c.6834C>T	p.Tyr2278Tyr	synonymous_variant	Exon 47 of 49		NP_001252541.1	A5YKK6-2
CNOT1	NR_049763.2 link	n.7290C>T		non_coding_transcript_exon_variant	Exon 48 of 50

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT1	ENST00000317147.10 link	c.6849C>T	p.Tyr2283Tyr	synonymous_variant	Exon 47 of 49	1	NM_016284.5	ENSP00000320949.5		A5YKK6-1
SETD6	ENST00000219315.9 link	c.*4409G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_001160305.4	ENSP00000219315.5		Q8TBK2-1

Frequencies

GnomAD3 genomes

AF:

0.0296

AC:

4511

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00835

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0299

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0482

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0285

AC:

7154

AN:

251434

Hom.:

147

AF XY:

0.0285

AC XY:

3877

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00751

Gnomad AMR exome

AF:

0.0203

Gnomad ASJ exome

AF:

0.0266

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00839

Gnomad FIN exome

AF:

0.0200

Gnomad NFE exome

AF:

0.0456

Gnomad OTH exome

AF:

0.0308

GnomAD4 exome

AF:

0.0406

AC:

59342

AN:

1461532

Hom.:

1372

Cov.:

AF XY:

0.0394

AC XY:

28676

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.00624

Gnomad4 AMR exome

AF:

0.0227

Gnomad4 ASJ exome

AF:

0.0276

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00814

Gnomad4 FIN exome

AF:

0.0214

Gnomad4 NFE exome

AF:

0.0479

Gnomad4 OTH exome

AF:

0.0366

GnomAD4 genome

AF:

0.0296

AC:

4510

AN:

152286

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2086

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00832

Gnomad4 AMR

AF:

0.0298

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00932

Gnomad4 FIN

AF:

0.0170

Gnomad4 NFE

AF:

0.0482

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0408

Hom.:

143

Bravo

AF:

0.0297

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0477

EpiControl

AF:

0.0493

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CNOT1-related disorder

Benign:1

Dec 11, 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

-0.44

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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