16-58543411-GAAA-G

Position:

• chr16-58543411-GAAA-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000441024.6(CNOT1):​c.4627_4629del​(p.Phe1543del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000492 in 1,218,522 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: 0.0000049 (0 hom.)
• Consequence: CNOT1 ENST00000441024.6 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNOT1	NM_016284.5	c.4434+193_4434+195del		intron_variant		ENST00000317147.10
CNOT1	NM_206999.3	c.4627_4629del	p.Phe1543del	inframe_deletion	31/31
CNOT1	NM_001265612.2	c.4419+193_4419+195del		intron_variant
CNOT1	NR_049763.2	n.4692+193_4692+195del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNOT1	ENST00000317147.10	c.4434+193_4434+195del		intron_variant		1	NM_016284.5	P3

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000492 AC: 6 AN: 1218522 Hom.: 0 AF XY: 0.00000841 AC XY: 5 AN XY: 594662

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000506

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000302

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000416

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs5817153; hg19: chr16-58577315;