rs174376

Positions:

• chr6-111587162-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TRAF3IP2	NM_147686.4	c.829+4096A>G		intron_variant		ENST00000368761.11	NP_679211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3IP2	ENST00000368761.11	c.829+4096A>G		intron_variant		1	NM_147686.4	ENSP00000357750.5

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110321 AN: 151968 Hom.: 40878 Cov.: 32

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: 5 AN: 8 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.667

GnomAD4 genome AF: 0.726 AC: 110407 AN: 152086 Hom.: 40911 Cov.: 32 AF XY: 0.723 AC XY: 53711 AN XY: 74334

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.800

Gnomad4 OTH AF: 0.764

Alfa AF: 0.782 Hom.: 15936

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
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs174376; hg19: chr6-111908365; COSMIC: COSV60677125; COSMIC: COSV60677125;