chr6-111591806-C-T

Variant names:

Variant summary

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

The NM_147686.4(TRAF3IP2):c.281G>A(p.Ser94Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,266 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 4 hom. )

Consequence

TRAF3IP2
NM_147686.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.56

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-AS1 (HGNC:40005): (TRAF3IP2 antisense RNA 1)

TRAF3IP2-AS1 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=0.005608052).

BP6

Variant 6-111591806-C-T is Benign according to our data. Variant chr6-111591806-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 541100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-111591806-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00109 (166/152374) while in subpopulation SAS AF= 0.00186 (9/4832). AF 95% confidence interval is 0.00115. There are 0 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP2	NM_147686.4 link	c.281G>A	p.Ser94Asn	missense_variant	Exon 2 of 9	ENST00000368761.11	NP_679211.2	O43734-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF3IP2	ENST00000368761.11 link	c.281G>A	p.Ser94Asn	missense_variant	Exon 2 of 9	1	NM_147686.4	ENSP00000357750.5		O43734-2

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00156

AC:

392

AN:

251446

Hom.:

AF XY:

0.00171

AC XY:

232

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00274

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00132

AC:

1924

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1027

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.0123

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00307

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152374

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.0132

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.000975

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00143

AC:

174

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TRAF3IP2: BP4, BS1, BS2 -

Candidiasis, familial, 8

Benign:1

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Psoriasis 13, susceptibility to;C3714992:Candidiasis, familial, 8

Benign:1

Jun 27, 2022

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF: 1.3% [130/10368], including in 2 homozygotes; https://gnomad.broadinstitute.org/variant/6-111913009-C-T?dataset=gnomad_r2_1 ), and in ClinVar, with multiple laboratories classifying it as benign (Variation ID: 541100). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;.;T;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.80

T;T;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.0056

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;.;L;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.79

N;N;N;.

REVEL

Benign

0.093

Sift

Uncertain

0.023

D;D;D;.

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.53

P;.;B;B

Vest4

0.29

MVP

0.53

MPC

0.36

ClinPred

0.0087

GERP RS

5.0

Varity_R

0.12

gMVP

0.31

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