Variant 19-54142930-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_014516.4(CNOT3):c.-49G>A variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00446 in 1,597,910 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 35 hom. )

Consequence

CNOT3
NM_014516.4 splice_region, 5_prime_UTR

Scores

Splicing: ADA: 0.002778

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.258

Variant links:

Genes affected

CNOT3 (HGNC:7879): (CCR4-NOT transcription complex subunit 3) Involved in regulation of stem cell population maintenance. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

CNOT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 19-54142930-G-A is Benign according to our data. Variant chr19-54142930-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1879454.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00412 (628/152264) while in subpopulation AMR AF= 0.0068 (104/15300). AF 95% confidence interval is 0.00574. There are 2 homozygotes in gnomad4. There are 318 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 628 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNOT3	NM_014516.4 linkuse as main transcript	c.-49G>A		splice_region_variant, 5_prime_UTR_variant	2/18	ENST00000221232.11	NP_055331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNOT3	ENST00000221232.11 linkuse as main transcript	c.-49G>A		splice_region_variant, 5_prime_UTR_variant	2/18	1	NM_014516.4	ENSP00000221232	P1

Frequencies

GnomAD3 genomes

AF:

0.00411

AC:

626

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00681

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00460

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00489

AC:

1224

AN:

250424

Hom.:

AF XY:

0.00524

AC XY:

710

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00662

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00519

Gnomad FIN exome

AF:

0.000909

Gnomad NFE exome

AF:

0.00500

Gnomad OTH exome

AF:

0.00914

GnomAD4 exome

AF:

0.00449

AC:

6492

AN:

1445646

Hom.:

Cov.:

AF XY:

0.00475

AC XY:

3423

AN XY:

720282

show subpopulations

Gnomad4 AFR exome

AF:

0.00205

Gnomad4 AMR exome

AF:

0.00680

Gnomad4 ASJ exome

AF:

0.0171

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00509

Gnomad4 FIN exome

AF:

0.000571

Gnomad4 NFE exome

AF:

0.00433

Gnomad4 OTH exome

AF:

0.00601

GnomAD4 genome

AF:

0.00412

AC:

628

AN:

152264

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

318

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.00680

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00460

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00546

Hom.:

Bravo

AF:

0.00458

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

CNOT3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0028

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