rs150601696

Positions:

chr6-111591850-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_147686.4(TRAF3IP2):c.237G>C(p.Gln79His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,614,214 control chromosomes in the GnomAD database, including 2 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 0.00055 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

TRAF3IP2
NM_147686.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.329

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0072900653).

BP6

Variant 6-111591850-C-G is Benign according to our data. Variant chr6-111591850-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 581633.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000551 (84/152328) while in subpopulation AMR AF= 0.00438 (67/15304). AF 95% confidence interval is 0.00354. There are 1 homozygotes in gnomad4. There are 46 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3IP2	NM_147686.4 linkuse as main transcript	c.237G>C	p.Gln79His	missense_variant	2/9	ENST00000368761.11	NP_679211.2
TRAF3IP2-AS1	NR_034108.1 linkuse as main transcript	n.486-5988C>G		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.237G>C	p.Gln79His	missense_variant	2/9	1	NM_147686.4	ENSP00000357750	P4	O43734-2
TRAF3IP2-AS1	ENST00000687951.2 linkuse as main transcript	n.446-5988C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000549

AC:

138

AN:

251444

Hom.:

AF XY:

0.000537

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000208

AC:

304

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

142

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00306

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000737

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000551

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000281

Hom.:

Bravo

AF:

0.00122

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000371

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Candidiasis, familial, 8

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

.;.;T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.59

T;T;.;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.0073

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;.;L;L

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.38

N;N;N;N

REVEL

Benign

0.032

Sift

Uncertain

0.025

D;D;D;D

Sift4G

Benign

0.41

T;T;T;T

Polyphen

0.0030

B;.;B;B

Vest4

0.19

MutPred

0.22

.;.;Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.49

MPC

0.18

ClinPred

0.0098

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.37

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