16-58543411-GAAA-GAAAAAA

Position:

• chr16-58543411-GAAA-GAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000317147.10(CNOT1):​c.4434+195_4434+196insTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,218,328 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: 0.000013 (0 hom.)
• Consequence: CNOT1 ENST00000317147.10 intron
• Clinical Significance: Not reported in ClinVar
• 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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000131 (16/1218328) while in subpopulation SAS AF= 0.0000665 (4/60120). AF 95% confidence interval is 0.0000225. There are 0 homozygotes in gnomad4_exome. There are 4 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNOT1	NM_016284.5	c.4434+195_4434+196insTTT		intron_variant		ENST00000317147.10	NP_057368.3
CNOT1	NM_206999.3	c.4629_4630insTTT	p.Phe1543dup	inframe_insertion	31/31		NP_996882.1
CNOT1	NM_001265612.2	c.4419+195_4419+196insTTT		intron_variant			NP_001252541.1
CNOT1	NR_049763.2	n.4692+195_4692+196insTTT		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+196insTTT		intron_variant		1	NM_016284.5	ENSP00000320949	P3

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD3 exomes AF: 0.0000735 AC: 5 AN: 68028 Hom.: 0 AF XY: 0.0000284 AC XY: 1 AN XY: 35246

Gnomad AFR exome AF: 0.000219

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000130

Gnomad FIN exome AF: 0.000120

Gnomad NFE exome AF: 0.0000374

Gnomad OTH exome AF: 0.000518

GnomAD4 exome AF: 0.0000131 AC: 16 AN: 1218328 Hom.: 0 Cov.: 0 AF XY: 0.00000673 AC XY: 4 AN XY: 594568

Gnomad4 AFR exome AF: 0.0000387

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000665

Gnomad4 FIN exome AF: 0.0000235

Gnomad4 NFE exome AF: 0.0000104

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;