rs174376

Variant names:

• chr6-111587162-T-C
• rs174376
• NM_147686.4:c.829+4096A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-111587162-T-C
• chr6-111587162-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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.

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.829+4096A>G		intron	N/A	NP_679211.2	O43734-2
	TRAF3IP2	NM_147200.3		c.856+4096A>G		intron	N/A	NP_671733.2	O43734-1
	TRAF3IP2	NM_001164281.3		c.829+4096A>G		intron	N/A	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.829+4096A>G		intron	N/A	ENSP00000357750.5	O43734-2
	TRAF3IP2	ENST00000340026.10	TSL:1	c.856+4096A>G		intron	N/A	ENSP00000345984.6	O43734-1
	TRAF3IP2	ENST00000528599.1	TSL:1	n.1024+4096A>G		intron	N/A

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

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 4 AN: 6

Other (OTH) AC: 0 AN: 0

⚠️ 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.

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.37
DANN	Benign	0.40
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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