dbSNP rs142054894: TRAF3IP2:p.Pro35dup (chr6-111591982-A-AGGT) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBS1BS2

The NM_147686.4(TRAF3IP2):c.102_104dupACC(p.Pro35dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00336 in 1,614,228 control chromosomes in the GnomAD database, including 64 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 61 hom. )

Consequence

TRAF3IP2
NM_147686.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.74

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_147686.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 6-111591982-A-AGGT is Benign according to our data. Variant chr6-111591982-A-AGGT is described in ClinVar as Benign. ClinVar VariationId is 541103.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0025 (381/152338) while in subpopulation EAS AF = 0.0222 (115/5188). AF 95% confidence interval is 0.0189. There are 3 homozygotes in GnomAd4. There are 191 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP2	NM_147686.4 link	c.102_104dupACC	p.Pro35dup	disruptive_inframe_insertion	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.102_104dupACC	p.Pro35dup	disruptive_inframe_insertion	Exon 2 of 9	1	NM_147686.4	ENSP00000357750.5		O43734-2

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

383

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0223

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00182

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00645

AC:

1620

AN:

251334

AF XY:

0.00540

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.0250

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.0228

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00165

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00344

AC:

5036

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

2441

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33480

American (AMR)

AF:

0.0218

AC:

974

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00245

AC:

AN:

26136

East Asian (EAS)

AF:

0.0389

AC:

1543

AN:

39700

South Asian (SAS)

AF:

0.00275

AC:

237

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00187

AC:

2082

AN:

1112010

Other (OTH)

AF:

0.00194

AC:

117

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

303

606

909

1212

1515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00250

AC:

381

AN:

152338

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

191

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41580

American (AMR)

AF:

0.00555

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.0222

AC:

115

AN:

5188

South Asian (SAS)

AF:

0.00394

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00182

AC:

124

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00291

Hom.:

Bravo

AF:

0.00368

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00213

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Candidiasis, familial, 8

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.7

Mutation Taster

=64/36

polymorphism

(source)

Splicing

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over