16-58543411-GAAA-GAAAAA

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM4BP6BS1BS2

The ENST00000441024.6(CNOT1):​c.4629_4630insTT​(p.Leu1544PhefsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000383 in 1,342,700 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000077 ( 0 hom., cov: 21)
Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

CNOT1
ENST00000441024.6 frameshift

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM4
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 1560 codons.
BP6
Variant 16-58543411-G-GAA is Benign according to our data. Variant chr16-58543411-G-GAA is described in ClinVar as [Likely_benign]. Clinvar id is 3060733.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000423 (513/1212824) while in subpopulation SAS AF= 0.00136 (81/59652). AF 95% confidence interval is 0.00112. There are 0 homozygotes in gnomad4_exome. There are 282 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 513 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CNOT1NM_016284.5 linkuse as main transcriptc.4434+195_4434+196insTT intron_variant ENST00000317147.10 NP_057368.3
CNOT1NM_206999.3 linkuse as main transcriptc.4629_4630insTT p.Leu1544PhefsTer12 frameshift_variant 31/31 NP_996882.1
CNOT1NM_001265612.2 linkuse as main transcriptc.4419+195_4419+196insTT intron_variant NP_001252541.1
CNOT1NR_049763.2 linkuse as main transcriptn.4692+195_4692+196insTT intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CNOT1ENST00000317147.10 linkuse as main transcriptc.4434+195_4434+196insTT intron_variant 1 NM_016284.5 ENSP00000320949 P3A5YKK6-1

Frequencies

GnomAD3 genomes
AF:
0.00000770
AC:
1
AN:
129810
Hom.:
0
Cov.:
21
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000136
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00215
AC:
146
AN:
68028
Hom.:
0
AF XY:
0.00221
AC XY:
78
AN XY:
35246
show subpopulations
Gnomad AFR exome
AF:
0.00306
Gnomad AMR exome
AF:
0.00190
Gnomad ASJ exome
AF:
0.00155
Gnomad EAS exome
AF:
0.00164
Gnomad SAS exome
AF:
0.00195
Gnomad FIN exome
AF:
0.00217
Gnomad NFE exome
AF:
0.00232
Gnomad OTH exome
AF:
0.00207
GnomAD4 exome
AF:
0.000423
AC:
513
AN:
1212824
Hom.:
0
Cov.:
0
AF XY:
0.000476
AC XY:
282
AN XY:
591866
show subpopulations
Gnomad4 AFR exome
AF:
0.000663
Gnomad4 AMR exome
AF:
0.00117
Gnomad4 ASJ exome
AF:
0.000780
Gnomad4 EAS exome
AF:
0.000395
Gnomad4 SAS exome
AF:
0.00136
Gnomad4 FIN exome
AF:
0.000946
Gnomad4 NFE exome
AF:
0.000308
Gnomad4 OTH exome
AF:
0.000558
GnomAD4 genome
AF:
0.00000770
AC:
1
AN:
129876
Hom.:
0
Cov.:
21
AF XY:
0.00
AC XY:
0
AN XY:
62590
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000136
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

CNOT1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 21, 2019This 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

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: rs5817153; hg19: chr16-58577315; API