Variant chr16-58532400-G-A 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.5896-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,610,182 control chromosomes in the GnomAD database, including 56,368 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4896 hom., cov: 33)

Exomes 𝑓: 0.26 ( 51472 hom. )

Consequence

CNOT1
NM_016284.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.000008593

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.590

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=-0.8).

BP6

Variant 16-58532400-G-A is Benign according to our data. Variant chr16-58532400-G-A is described in ClinVar as [Benign]. Clinvar id is 1217372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CNOT1	NM_016284.5 linkuse as main transcript	c.5896-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000317147.10	NP_057368.3
CNOT1	NM_001265612.2 linkuse as main transcript	c.5881-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001252541.1
CNOT1	NR_049763.2 linkuse as main transcript	n.6154-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNOT1	ENST00000317147.10 linkuse as main transcript	c.5896-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_016284.5	ENSP00000320949	P3	A5YKK6-1

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36906

AN:

151982

Hom.:

4881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.231

GnomAD3 exomes

AF:

0.291

AC:

72945

AN:

250324

Hom.:

11647

AF XY:

0.286

AC XY:

38771

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.452

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.384

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.260

AC:

379032

AN:

1458080

Hom.:

51472

Cov.:

AF XY:

0.261

AC XY:

189096

AN XY:

724590

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.438

Gnomad4 ASJ exome

AF:

0.257

Gnomad4 EAS exome

AF:

0.354

Gnomad4 SAS exome

AF:

0.319

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.248

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.243

AC:

36948

AN:

152102

Hom.:

4896

Cov.:

AF XY:

0.247

AC XY:

18368

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.349

Gnomad4 ASJ

AF:

0.257

Gnomad4 EAS

AF:

0.381

Gnomad4 SAS

AF:

0.336

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.251

Gnomad4 OTH

AF:

0.235

Alfa

AF:

0.258

Hom.:

6211

Bravo

AF:

0.245

Asia WGS

AF:

0.353

AC:

1229

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Vissers-Bodmer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Holoprosencephaly 12 with or without pancreatic agenesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.4

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000086

dbscSNV1_RF

Benign

0.0

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