chr6-111591867-G-A

Position:

chr6-111591867-G-A

Variant summary

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

The ENST00000368761.11(TRAF3IP2):c.220C>T(p.Arg74Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,614,154 control chromosomes in the GnomAD database, including 2,724 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R74Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.050 ( 208 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2516 hom. )

Consequence

TRAF3IP2
ENST00000368761.11 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.937

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=0.0018520057).

BP6

Variant 6-111591867-G-A is Benign according to our data. Variant chr6-111591867-G-A is described in ClinVar as [Benign]. Clinvar id is 403566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0569 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.220C>T	p.Arg74Trp	missense_variant	2/9	ENST00000368761.11	NP_679211.2
TRAF3IP2-AS1	NR_034108.1 linkuse as main transcript	n.486-5971G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3IP2	ENST00000368761.11 linkuse as main transcript	c.220C>T	p.Arg74Trp	missense_variant	2/9	1	NM_147686.4	ENSP00000357750	P4	O43734-2
TRAF3IP2-AS1	ENST00000687951.2 linkuse as main transcript	n.446-5971G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0497

AC:

7567

AN:

152154

Hom.:

210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0374

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.0483

Gnomad ASJ

AF:

0.0888

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0369

Gnomad FIN

AF:

0.0565

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0584

Gnomad OTH

AF:

0.0583

GnomAD3 exomes

AF:

0.0531

AC:

13359

AN:

251428

Hom.:

394

AF XY:

0.0535

AC XY:

7270

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0363

Gnomad AMR exome

AF:

0.0598

Gnomad ASJ exome

AF:

0.0949

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0463

Gnomad FIN exome

AF:

0.0613

Gnomad NFE exome

AF:

0.0582

Gnomad OTH exome

AF:

0.0619

GnomAD4 exome

AF:

0.0565

AC:

82586

AN:

1461882

Hom.:

2516

Cov.:

AF XY:

0.0565

AC XY:

41098

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0372

Gnomad4 AMR exome

AF:

0.0599

Gnomad4 ASJ exome

AF:

0.0962

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0475

Gnomad4 FIN exome

AF:

0.0618

Gnomad4 NFE exome

AF:

0.0585

Gnomad4 OTH exome

AF:

0.0562

GnomAD4 genome

AF:

0.0497

AC:

7570

AN:

152272

Hom.:

208

Cov.:

AF XY:

0.0482

AC XY:

3590

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0373

Gnomad4 AMR

AF:

0.0483

Gnomad4 ASJ

AF:

0.0888

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0375

Gnomad4 FIN

AF:

0.0565

Gnomad4 NFE

AF:

0.0584

Gnomad4 OTH

AF:

0.0572

Alfa

AF:

0.0578

Hom.:

602

Bravo

AF:

0.0493

TwinsUK

AF:

0.0547

AC:

203

ALSPAC

AF:

0.0568

AC:

219

ESP6500AA

AF:

0.0361

AC:

159

ESP6500EA

AF:

0.0597

AC:

513

ExAC

AF:

0.0509

AC:

6178

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0598

EpiControl

AF:

0.0576

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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

- -

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

0.058

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.030

.;.;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.74

T;T;.;T

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

.;.;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.16

PROVEAN

Benign

0.66

N;N;N;.

REVEL

Benign

0.025

Sift

Benign

0.052

T;T;T;.

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.086

MPC

0.20

ClinPred

0.0045

GERP RS

-5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.14

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