Variant 22-41436557-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016272.4(TOB2):c.789C>T(p.Asn263Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00488 in 1,609,368 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 87 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 119 hom. )

Consequence

TOB2
NM_016272.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.43

Variant links:

Genes affected

TOB2 (HGNC:11980): (transducer of ERBB2, 2) TOB2 belongs to the TOB (see TOB1; MIM 605523)/BTG1 (MIM 109580) family of antiproliferative proteins, which are involved in the regulation of cell cycle progression.[supplied by OMIM, Apr 2004]

TOB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 22-41436557-G-A is Benign according to our data. Variant chr22-41436557-G-A is described in ClinVar as [Benign]. Clinvar id is 784421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOB2	NM_016272.4 link	c.789C>T	p.Asn263Asn	synonymous_variant	2/2	ENST00000327492.4	NP_057356.1	Q14106-1
TOB2	XM_005261315.3 link	c.789C>T	p.Asn263Asn	synonymous_variant	2/2		XP_005261372.1	Q14106-1
TOB2	XM_006724105.4 link	c.789C>T	p.Asn263Asn	synonymous_variant	2/2		XP_006724168.1	Q14106-1
TOB2	XM_017028539.2 link	c.789C>T	p.Asn263Asn	synonymous_variant	2/2		XP_016884028.1	Q14106-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOB2	ENST00000327492.4 link	c.789C>T	p.Asn263Asn	synonymous_variant	2/2	1	NM_016272.4	ENSP00000331305.3		Q14106-1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2913

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.00652

AC:

1540

AN:

236278

Hom.:

AF XY:

0.00531

AC XY:

681

AN XY:

128292

show subpopulations

Gnomad AFR exome

AF:

0.0595

Gnomad AMR exome

AF:

0.00556

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.000593

Gnomad NFE exome

AF:

0.00187

Gnomad OTH exome

AF:

0.00564

GnomAD4 exome

AF:

0.00338

AC:

4928

AN:

1457008

Hom.:

119

Cov.:

AF XY:

0.00321

AC XY:

2324

AN XY:

724502

show subpopulations

Gnomad4 AFR exome

AF:

0.0696

Gnomad4 AMR exome

AF:

0.00638

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00148

Gnomad4 FIN exome

AF:

0.000715

Gnomad4 NFE exome

AF:

0.000968

Gnomad4 OTH exome

AF:

0.00813

GnomAD4 genome

AF:

0.0192

AC:

2918

AN:

152360

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1353

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0604

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00154

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.0218

Asia WGS

AF:

0.00751

AC:

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.86

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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