rs33980500

Variant names:

• chr6-111592059-C-T
• rs33980500
• NM_147686.4:c.28G>A
• TRAF3IP2 p.Asp10Asn

Your query was ambiguous. Multiple possible variants found:

• chr6-111592059-C-T
• chr6-111592059-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_147686.4(TRAF3IP2):​c.28G>A​(p.Asp10Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0791 in 1,613,952 control chromosomes in the GnomAD database, including 5,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (820 hom., cov: 32)
  • Exomes 𝑓: 0.077 (4778 hom.)
• Consequence: TRAF3IP2 NM_147686.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:2
• Conservation: PhyloP100: 5.11
• Publications: 149 publications found

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-AS1 (HGNC:40005): (TRAF3IP2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017044842).
• BP6: Variant 6-111592059-C-T is Benign according to our data. Variant chr6-111592059-C-T is described in ClinVar as Benign. ClinVar VariationId is 30630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147686.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP2	NM_147686.4	MANE Select	c.28G>A	p.Asp10Asn	missense	Exon 2 of 9	NP_679211.2	O43734-2
	TRAF3IP2	NM_147200.3		c.55G>A	p.Asp19Asn	missense	Exon 3 of 10	NP_671733.2	O43734-1
	TRAF3IP2	NM_001164281.3		c.28G>A	p.Asp10Asn	missense	Exon 2 of 9	NP_001157753.1	O43734-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP2	ENST00000368761.11	TSL:1 MANE Select	c.28G>A	p.Asp10Asn	missense	Exon 2 of 9	ENSP00000357750.5	O43734-2
	TRAF3IP2	ENST00000340026.10	TSL:1	c.55G>A	p.Asp19Asn	missense	Exon 3 of 10	ENSP00000345984.6	O43734-1
	TRAF3IP2	ENST00000528599.1	TSL:1	n.223G>A		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14493 AN: 152154 Hom.: 821 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.00653

Gnomad SAS AF: 0.0579

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.0856 AC: 21353 AN: 249574 AF XY: 0.0818

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.00228

Gnomad FIN exome AF: 0.0724

Gnomad NFE exome AF: 0.0745

Gnomad OTH exome AF: 0.0887

GnomAD4 exome AF: 0.0774 AC: 113140 AN: 1461680 Hom.: 4778 Cov.: 31 AF XY: 0.0771 AC XY: 56048 AN XY: 727130

African (AFR) AF: 0.142 AC: 4764 AN: 33472

American (AMR) AF: 0.138 AC: 6180 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3670 AN: 26128

East Asian (EAS) AF: 0.0115 AC: 455 AN: 39700

South Asian (SAS) AF: 0.0701 AC: 6044 AN: 86238

European-Finnish (FIN) AF: 0.0721 AC: 3854 AN: 53420

Middle Eastern (MID) AF: 0.0995 AC: 574 AN: 5768

European-Non Finnish (NFE) AF: 0.0743 AC: 82651 AN: 1111846

Other (OTH) AF: 0.0819 AC: 4948 AN: 60388

GnomAD4 genome AF: 0.0953 AC: 14508 AN: 152272 Hom.: 820 Cov.: 32 AF XY: 0.0928 AC XY: 6911 AN XY: 74460

African (AFR) AF: 0.145 AC: 6014 AN: 41528

American (AMR) AF: 0.112 AC: 1707 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3472

East Asian (EAS) AF: 0.00655 AC: 34 AN: 5194

South Asian (SAS) AF: 0.0588 AC: 284 AN: 4830

European-Finnish (FIN) AF: 0.0654 AC: 694 AN: 10616

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0736 AC: 5008 AN: 68014

Other (OTH) AF: 0.102 AC: 216 AN: 2116

Alfa AF: 0.0785 Hom.: 1770

Bravo AF: 0.102

Asia WGS AF: 0.0420 AC: 148 AN: 3478

EpiCase AF: 0.0769

EpiControl AF: 0.0736

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Candidiasis, familial, 8 (1)
-	-	-	not provided (1)
-	-	-	Psoriasis 13, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.1
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.14	T
Varity_R		0.38
gMVP		0.36
Mutation Taster		=295/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs33980500;

hg19: chr6-111913262;

COSMIC: COSV60675431;

COSMIC: COSV60675431;