Variant 16-58525085-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016284.5(CNOT1):c.6784+94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,152,990 control chromosomes in the GnomAD database, including 42,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5033 hom., cov: 32)

Exomes 𝑓: 0.27 ( 37551 hom. )

Consequence

CNOT1
NM_016284.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0260

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-58525085-C-T is Benign according to our data. Variant chr16-58525085-C-T is described in ClinVar as [Benign]. Clinvar id is 1226579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CNOT1	NM_016284.5 linkuse as main transcript	c.6784+94G>A	intron_variant	ENST00000317147.10
CNOT1	NM_001265612.2 linkuse as main transcript	c.6769+94G>A	intron_variant
CNOT1	NR_049763.2 linkuse as main transcript	n.7225+94G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNOT1	ENST00000317147.10 linkuse as main transcript	c.6784+94G>A		intron_variant		1	NM_016284.5	P3	A5YKK6-1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37444

AN:

151990

Hom.:

5018

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.239

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.232

GnomAD4 exome

AF:

0.267

AC:

267320

AN:

1000882

Hom.:

37551

AF XY:

0.267

AC XY:

136672

AN XY:

511170

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.432

Gnomad4 ASJ exome

AF:

0.254

Gnomad4 EAS exome

AF:

0.351

Gnomad4 SAS exome

AF:

0.316

Gnomad4 FIN exome

AF:

0.294

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.246

AC:

37485

AN:

152108

Hom.:

5033

Cov.:

AF XY:

0.252

AC XY:

18749

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.349

Gnomad4 ASJ

AF:

0.257

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.336

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.254

Gnomad4 OTH

AF:

0.237

Alfa

AF:

0.251

Hom.:

848

Bravo

AF:

0.246

Asia WGS

AF:

0.353

AC:

1230

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

DANN

Benign

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over