Genetic Variant ENST00000441024.6:c.4624_4629delTTTTTT (chr16-58543411-GAAAAAA-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
Vissers-Bodmer syndrome
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

CNOT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in ENST00000441024.6

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441024.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNOT1	NM_016284.5	MANE Select	c.4434+190_4434+195delTTTTTT		intron	N/A	NP_057368.3
CNOT1	NM_206999.3		c.4624_4629delTTTTTT	p.Phe1542_Phe1543del	conservative_inframe_deletion	Exon 31 of 31	NP_996882.1	A5YKK6-4
CNOT1	NM_001265612.2		c.4419+190_4419+195delTTTTTT		intron	N/A	NP_001252541.1	A5YKK6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNOT1	ENST00000441024.6	TSL:1	c.4624_4629delTTTTTT	p.Phe1542_Phe1543del	conservative_inframe_deletion	Exon 31 of 31	ENSP00000413113.2	A5YKK6-4
CNOT1	ENST00000317147.10	TSL:1 MANE Select	c.4434+190_4434+195delTTTTTT		intron	N/A	ENSP00000320949.5	A5YKK6-1
CNOT1	ENST00000569240.5	TSL:1	c.4419+190_4419+195delTTTTTT		intron	N/A	ENSP00000455635.1	A5YKK6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.21e-7

AC:

AN:

1218550

Hom.:

AF XY:

0.00000168

AC XY:

AN XY:

594676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25830

American (AMR)

AF:

0.00

AC:

AN:

19756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19356

East Asian (EAS)

AF:

0.00

AC:

AN:

33088

South Asian (SAS)

AF:

0.00

AC:

AN:

60144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4784

European-Non Finnish (NFE)

AF:

0.00000104

AC:

AN:

962672

Other (OTH)

AF:

0.00

AC:

AN:

50422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.8

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over