16-58543411-GAAA-GAAAAA
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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
ENST00000441024.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0160
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 |
---|---|---|---|---|---|---|---|---|
CNOT1 | NM_016284.5 | c.4434+195_4434+196insTT | intron_variant | ENST00000317147.10 | NP_057368.3 | |||
CNOT1 | NM_206999.3 | c.4629_4630insTT | p.Leu1544PhefsTer12 | frameshift_variant | 31/31 | NP_996882.1 | ||
CNOT1 | NM_001265612.2 | c.4419+195_4419+196insTT | intron_variant | NP_001252541.1 | ||||
CNOT1 | NR_049763.2 | n.4692+195_4692+196insTT | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNOT1 | ENST00000317147.10 | c.4434+195_4434+196insTT | intron_variant | 1 | NM_016284.5 | ENSP00000320949 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00000770 AC: 1AN: 129810Hom.: 0 Cov.: 21
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GnomAD3 exomes AF: 0.00215 AC: 146AN: 68028Hom.: 0 AF XY: 0.00221 AC XY: 78AN XY: 35246
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GnomAD4 exome AF: 0.000423 AC: 513AN: 1212824Hom.: 0 Cov.: 0 AF XY: 0.000476 AC XY: 282AN XY: 591866
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GnomAD4 genome AF: 0.00000770 AC: 1AN: 129876Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 62590
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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 provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 21, 2019 | 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
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at