6-111580250-G-T

Position:

chr6-111580250-G-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.969C>A(p.His323Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,614,006 control chromosomes in the GnomAD database, including 528,557 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 (★★).

Frequency

Genomes: 𝑓 0.85 ( 56204 hom., cov: 34)

Exomes 𝑓: 0.80 ( 472353 hom. )

Consequence

TRAF3IP2
NM_147686.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.260

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=5.539725E-7).

BP6

Variant 6-111580250-G-T is Benign according to our data. Variant chr6-111580250-G-T is described in ClinVar as [Benign]. Clinvar id is 403565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.969C>A	p.His323Gln	missense_variant	3/9	ENST00000368761.11	NP_679211.2
TRAF3IP2-AS1	NR_034108.1 linkuse as main transcript	n.485+3780G>T		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.969C>A	p.His323Gln	missense_variant	3/9	1	NM_147686.4	ENSP00000357750	P4	O43734-2
TRAF3IP2-AS1	ENST00000687951.2 linkuse as main transcript	n.445+3780G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.855

AC:

130068

AN:

152180

Hom.:

56133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.961

Gnomad AMI

AF:

0.860

Gnomad AMR

AF:

0.857

Gnomad ASJ

AF:

0.777

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.936

Gnomad FIN

AF:

0.854

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.778

Gnomad OTH

AF:

0.840

GnomAD3 exomes

AF:

0.852

AC:

213609

AN:

250782

Hom.:

91840

AF XY:

0.849

AC XY:

115041

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.966

Gnomad AMR exome

AF:

0.902

Gnomad ASJ exome

AF:

0.783

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.935

Gnomad FIN exome

AF:

0.844

Gnomad NFE exome

AF:

0.783

Gnomad OTH exome

AF:

0.819

GnomAD4 exome

AF:

0.801

AC:

1171133

AN:

1461708

Hom.:

472353

Cov.:

AF XY:

0.805

AC XY:

585086

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.966

Gnomad4 AMR exome

AF:

0.899

Gnomad4 ASJ exome

AF:

0.782

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.934

Gnomad4 FIN exome

AF:

0.840

Gnomad4 NFE exome

AF:

0.773

Gnomad4 OTH exome

AF:

0.810

GnomAD4 genome

AF:

0.855

AC:

130199

AN:

152298

Hom.:

56204

Cov.:

AF XY:

0.860

AC XY:

64056

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.961

Gnomad4 AMR

AF:

0.857

Gnomad4 ASJ

AF:

0.777

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.936

Gnomad4 FIN

AF:

0.854

Gnomad4 NFE

AF:

0.778

Gnomad4 OTH

AF:

0.842

Alfa

AF:

0.790

Hom.:

117688

Bravo

AF:

0.858

ESP6500AA

AF:

0.959

AC:

4224

ESP6500EA

AF:

0.778

AC:

6695

ExAC

AF:

0.853

AC:

103599

Asia WGS

AF:

0.964

AC:

3352

AN:

3478

EpiCase

AF:

0.765

EpiControl

AF:

0.772

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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: Frequency -
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 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

Candidiasis, familial, 8

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 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

0.057

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.6

DANN

Benign

0.82

DEOGEN2

Benign

0.027

.;.;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.080

T;T;.;T

MetaRNN

Benign

5.5e-7

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.5

.;.;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

0.65

N;N;N;.

REVEL

Benign

0.060

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.043

MutPred

0.17

.;.;Gain of relative solvent accessibility (P = 0.0999);Gain of relative solvent accessibility (P = 0.0999);

MPC

0.19

ClinPred

0.0024

GERP RS

3.5

Varity_R

0.036

gMVP

0.089

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