Genetic Variant TRAF3IP2:c.829+4096A>G (chr6-111587162-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_147686.4(TRAF3IP2):c.829+4096A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,094 control chromosomes in the GnomAD database, including 40,913 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.73 ( 40911 hom., cov: 32)

Exomes 𝑓: 0.63 ( 2 hom. )

Consequence

TRAF3IP2
NM_147686.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.929

Publications

4 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP2	NM_147686.4 link	c.829+4096A>G		intron_variant	Intron 2 of 8	ENST00000368761.11	NP_679211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF3IP2	ENST00000368761.11 link	c.829+4096A>G		intron_variant	Intron 2 of 8	1	NM_147686.4	ENSP00000357750.5

Frequencies

GnomAD3 genomes

AF:

0.726

AC:

110321

AN:

151968

Hom.:

40878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.593

Gnomad AMI

AF:

0.685

Gnomad AMR

AF:

0.809

Gnomad ASJ

AF:

0.774

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.728

Gnomad FIN

AF:

0.725

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.800

Gnomad OTH

AF:

0.765

GnomAD4 exome

AF:

0.625

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.726

AC:

110407

AN:

152086

Hom.:

40911

Cov.:

AF XY:

0.723

AC XY:

53711

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.593

AC:

24594

AN:

41464

American (AMR)

AF:

0.809

AC:

12370

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.774

AC:

2685

AN:

3468

East Asian (EAS)

AF:

0.530

AC:

2743

AN:

5180

South Asian (SAS)

AF:

0.728

AC:

3502

AN:

4808

European-Finnish (FIN)

AF:

0.725

AC:

7664

AN:

10566

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.800

AC:

54389

AN:

67998

Other (OTH)

AF:

0.764

AC:

1611

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1470

2940

4411

5881

7351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.778

Hom.:

19558

Bravo

AF:

0.730

Asia WGS

AF:

0.667

AC:

2322

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.37

(source)

DANN

Benign

0.40

PhyloP100

-0.93

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over