GeneBe

ENST00000441024.6:c.4624_4629delTTTTTT

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000441024.6(CNOT1):​c.4624_4629delTTTTTT​(p.Phe1542_Phe1543del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000000821 in 1,218,550 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 21)
Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

CNOT1
ENST00000441024.6 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.77

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • holoprosencephaly 12 with or without pancreatic agenesis
    Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
  • Vissers-Bodmer syndrome
    Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNOT1NM_016284.5 linkc.4434+190_4434+195delTTTTTT intron_variant Intron 31 of 48 ENST00000317147.10 NP_057368.3 A5YKK6-1
CNOT1NM_206999.3 linkc.4624_4629delTTTTTT p.Phe1542_Phe1543del conservative_inframe_deletion Exon 31 of 31 NP_996882.1 A5YKK6-4
CNOT1NM_001265612.2 linkc.4419+190_4419+195delTTTTTT intron_variant Intron 31 of 48 NP_001252541.1 A5YKK6-2
CNOT1NR_049763.2 linkn.4692+190_4692+195delTTTTTT intron_variant Intron 31 of 49

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNOT1ENST00000317147.10 linkc.4434+190_4434+195delTTTTTT intron_variant Intron 31 of 48 1 NM_016284.5 ENSP00000320949.5 A5YKK6-1

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD4 exome
AF:
8.21e-7
AC:
1
AN:
1218550
Hom.:
0
AF XY:
0.00000168
AC XY:
1
AN XY:
594676
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
25830
American (AMR)
AF:
0.00
AC:
0
AN:
19756
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19356
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33088
South Asian (SAS)
AF:
0.00
AC:
0
AN:
60144
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
42498
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4784
European-Non Finnish (NFE)
AF:
0.00000104
AC:
1
AN:
962672
Other (OTH)
AF:
0.00
AC:
0
AN:
50422
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs5817153; hg19: chr16-58577315; API