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GeneBe

16-58523438-G-A

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.Tyr2283=) 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

2

Clinical Significance

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

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]
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]

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/exons MANE UniProt
CNOT1NM_016284.5 linkuse as main transcriptc.6849C>T p.Tyr2283= synonymous_variant 47/49 ENST00000317147.10
SETD6NM_001160305.4 linkuse as main transcriptc.*4409G>A 3_prime_UTR_variant 8/8 ENST00000219315.9
CNOT1NM_001265612.2 linkuse as main transcriptc.6834C>T p.Tyr2278= synonymous_variant 47/49
CNOT1NR_049763.2 linkuse as main transcriptn.7290C>T non_coding_transcript_exon_variant 48/50

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CNOT1ENST00000317147.10 linkuse as main transcriptc.6849C>T p.Tyr2283= synonymous_variant 47/491 NM_016284.5 P3A5YKK6-1
SETD6ENST00000219315.9 linkuse as main transcriptc.*4409G>A 3_prime_UTR_variant 8/81 NM_001160305.4 Q8TBK2-1
ENST00000622896.1 linkuse as main transcriptn.469G>A non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.0296
AC:
4511
AN:
152168
Hom.:
84
Cov.:
32
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.:
31
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.:
84
Cov.:
32
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:
19
AN:
3478
EpiCase
AF:
0.0477
EpiControl
AF:
0.0493

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 30, 2024- -
CNOT1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesDec 11, 2019This 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
18
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.

Other links and lift over

dbSNP: rs11644694; hg19: chr16-58557342; API