6-111592059-C-T

Position:

chr6-111592059-C-T

Variant summary

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

The NM_147686.4(TRAF3IP2):c.28G>A(p.Asp10Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0791 in 1,613,952 control chromosomes in the GnomAD database, including 5,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 820 hom., cov: 32)

Exomes 𝑓: 0.077 ( 4778 hom. )

Consequence

TRAF3IP2
NM_147686.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:2

Conservation

PhyloP100: 5.11

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=0.0017044842).

BP6

Variant 6-111592059-C-T is Benign according to our data. Variant chr6-111592059-C-T is described in ClinVar as [Benign]. Clinvar id is 30630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3IP2	NM_147686.4 linkuse as main transcript	c.28G>A	p.Asp10Asn	missense_variant	2/9	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.28G>A	p.Asp10Asn	missense_variant	2/9	1	NM_147686.4	ENSP00000357750.5		O43734-2

Frequencies

GnomAD3 genomes

AF:

0.0953

AC:

14493

AN:

152154

Hom.:

821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.00653

Gnomad SAS

AF:

0.0579

Gnomad FIN

AF:

0.0654

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0736

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.0856

AC:

21353

AN:

249574

Hom.:

1097

AF XY:

0.0818

AC XY:

11055

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.00228

Gnomad SAS exome

AF:

0.0703

Gnomad FIN exome

AF:

0.0724

Gnomad NFE exome

AF:

0.0745

Gnomad OTH exome

AF:

0.0887

GnomAD4 exome

AF:

0.0774

AC:

113140

AN:

1461680

Hom.:

4778

Cov.:

AF XY:

0.0771

AC XY:

56048

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.0115

Gnomad4 SAS exome

AF:

0.0701

Gnomad4 FIN exome

AF:

0.0721

Gnomad4 NFE exome

AF:

0.0743

Gnomad4 OTH exome

AF:

0.0819

GnomAD4 genome

AF:

0.0953

AC:

14508

AN:

152272

Hom.:

820

Cov.:

AF XY:

0.0928

AC XY:

6911

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.145

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.00655

Gnomad4 SAS

AF:

0.0588

Gnomad4 FIN

AF:

0.0654

Gnomad4 NFE

AF:

0.0736

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0755

Hom.:

799

Bravo

AF:

0.102

TwinsUK

AF:

0.0709

AC:

263

ALSPAC

AF:

0.0719

AC:

277

ESP6500AA

AF:

0.140

AC:

619

ESP6500EA

AF:

0.0774

AC:

666

ExAC

AF:

0.0822

AC:

9978

Asia WGS

AF:

0.0420

AC:

148

AN:

3478

EpiCase

AF:

0.0769

EpiControl

AF:

0.0736

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Candidiasis, familial, 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Psoriasis 13, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Oct 17, 2013

- -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

.;.;T;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.89

D;D;.;D

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.0

.;.;M;M

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.5

N;N;N;.

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;D;D;.

Sift4G

Benign

0.14

T;T;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.67

MPC

0.75

ClinPred

0.026

GERP RS

5.5

Varity_R

0.38

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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