rs139767840

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_147686.4(TRAF3IP2):c.1184A>G(p.Asn395Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00269 in 1,611,662 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 13 hom. )

Consequence

TRAF3IP2
NM_147686.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.64

Variant links:

Genes affected

TRAF3IP2 (HGNC:1343): (TRAF3 interacting protein 2) This gene encodes a protein involved in regulating responses to cytokines by members of the Rel/NF-kappaB transcription factor family. These factors play a central role in innate immunity in response to pathogens, inflammatory signals and stress. This gene product interacts with TRAF proteins (tumor necrosis factor receptor-associated factors) and either I-kappaB kinase or MAP kinase to activate either NF-kappaB or Jun kinase. Several alternative transcripts encoding different isoforms have been identified. Another transcript, which does not encode a protein and is transcribed in the opposite orientation, has been identified. Overexpression of this transcript has been shown to reduce expression of at least one of the protein encoding transcripts, suggesting it has a regulatory role in the expression of this gene. [provided by RefSeq, Aug 2009]

TRAF3IP2 links:

TRAF3IP2 (HGNC:):

TRAF3IP2 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 (MetaRNN=0.010694742).

BP6

Variant 6-111575660-T-C is Benign according to our data. Variant chr6-111575660-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 541102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-111575660-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00173 (262/151300) while in subpopulation NFE AF= 0.00302 (205/67886). AF 95% confidence interval is 0.00268. There are 1 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3IP2	NM_147686.4 linkuse as main transcript	c.1184A>G	p.Asn395Ser	missense_variant	4/9	ENST00000368761.11	NP_679211.2	O43734-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3IP2	ENST00000368761.11 linkuse as main transcript	c.1184A>G	p.Asn395Ser	missense_variant	4/9	1	NM_147686.4	ENSP00000357750.5		O43734-2

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

262

AN:

151230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000487

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.000987

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000485

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.00302

Gnomad OTH

AF:

0.00241

GnomAD3 exomes

AF:

0.00217

AC:

544

AN:

250694

Hom.:

AF XY:

0.00234

AC XY:

317

AN XY:

135548

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000812

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00281

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.00353

Gnomad OTH exome

AF:

0.000982

GnomAD4 exome

AF:

0.00279

AC:

4078

AN:

1460362

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

2025

AN XY:

726540

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.000897

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00284

Gnomad4 FIN exome

AF:

0.000675

Gnomad4 NFE exome

AF:

0.00318

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00173

AC:

262

AN:

151300

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

118

AN XY:

73858

show subpopulations

Gnomad4 AFR

AF:

0.000486

Gnomad4 AMR

AF:

0.000985

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00167

Gnomad4 FIN

AF:

0.000485

Gnomad4 NFE

AF:

0.00302

Gnomad4 OTH

AF:

0.00239

Alfa

AF:

0.00267

Hom.:

Bravo

AF:

0.00170

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00241

AC:

293

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00436

EpiControl

AF:

0.00303

ClinVar

Significance: Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Candidiasis, familial, 8

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

TRAF3IP2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;.;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

D;D;.;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

.;.;M;M

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.4

N;N;N;.

REVEL

Benign

0.10

Sift

Benign

0.037

D;D;D;.

Sift4G

Benign

0.12

T;T;T;T

Polyphen

1.0

D;.;D;D

Vest4

0.33

MVP

0.46

MPC

0.32

ClinPred

0.026

GERP RS

5.6

Varity_R

0.17

gMVP

0.28

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