rs13190932

Variant names:

• chr6-111591867-G-A
• rs13190932
• NM_147686.4:c.220C>T

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.220C>T​(p.Arg74Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,614,154 control chromosomes in the GnomAD database, including 2,724 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R74Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.050 (208 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2516 hom.)
• Consequence: TRAF3IP2 NM_147686.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.937
• Publications: 55 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=0.0018520057).
• BP6: Variant 6-111591867-G-A is Benign according to our data. Variant chr6-111591867-G-A is described in ClinVar as Benign. ClinVar VariationId is 403566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0569 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.220C>T	p.Arg74Trp	missense	Exon 2 of 9	NP_679211.2	O43734-2
	TRAF3IP2	NM_147200.3		c.247C>T	p.Arg83Trp	missense	Exon 3 of 10	NP_671733.2	O43734-1
	TRAF3IP2	NM_001164281.3		c.220C>T	p.Arg74Trp	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.220C>T	p.Arg74Trp	missense	Exon 2 of 9	ENSP00000357750.5	O43734-2
	TRAF3IP2	ENST00000340026.10	TSL:1	c.247C>T	p.Arg83Trp	missense	Exon 3 of 10	ENSP00000345984.6	O43734-1
	TRAF3IP2	ENST00000528599.1	TSL:1	n.415C>T		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7567 AN: 152154 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0483

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0369

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0584

Gnomad OTH AF: 0.0583

GnomAD2 exomes AF: 0.0531 AC: 13359 AN: 251428 AF XY: 0.0535

Gnomad AFR exome AF: 0.0363

Gnomad AMR exome AF: 0.0598

Gnomad ASJ exome AF: 0.0949

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.0613

Gnomad NFE exome AF: 0.0582

Gnomad OTH exome AF: 0.0619

GnomAD4 exome AF: 0.0565 AC: 82586 AN: 1461882 Hom.: 2516 Cov.: 31 AF XY: 0.0565 AC XY: 41098 AN XY: 727246

African (AFR) AF: 0.0372 AC: 1244 AN: 33478

American (AMR) AF: 0.0599 AC: 2679 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 2515 AN: 26136

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.0475 AC: 4098 AN: 86258

European-Finnish (FIN) AF: 0.0618 AC: 3299 AN: 53420

Middle Eastern (MID) AF: 0.0602 AC: 347 AN: 5768

European-Non Finnish (NFE) AF: 0.0585 AC: 64998 AN: 1112002

Other (OTH) AF: 0.0562 AC: 3394 AN: 60396

GnomAD4 genome AF: 0.0497 AC: 7570 AN: 152272 Hom.: 208 Cov.: 32 AF XY: 0.0482 AC XY: 3590 AN XY: 74448

African (AFR) AF: 0.0373 AC: 1552 AN: 41556

American (AMR) AF: 0.0483 AC: 739 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 308 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0375 AC: 181 AN: 4824

European-Finnish (FIN) AF: 0.0565 AC: 599 AN: 10600

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0584 AC: 3971 AN: 68022

Other (OTH) AF: 0.0572 AC: 121 AN: 2114

Alfa AF: 0.0564 Hom.: 848

Bravo AF: 0.0493

TwinsUK AF: 0.0547 AC: 203

ALSPAC AF: 0.0568 AC: 219

ESP6500AA AF: 0.0361 AC: 159

ESP6500EA AF: 0.0597 AC: 513

ExAC AF: 0.0509 AC: 6178

Asia WGS AF: 0.0210 AC: 75 AN: 3478

EpiCase AF: 0.0598

EpiControl AF: 0.0576

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Candidiasis, familial, 8 (1)
-	-	1	not specified (1)
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.77
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.94
PrimateAI	Benign	0.16	T
PROVEAN	Benign	0.66	N
REVEL	Benign	0.025
Sift	Benign	0.052	T
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.086
MPC		0.20
ClinPred		0.0045	T
GERP RS		-5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.14
Mutation Taster		=98/2	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: rs13190932; hg19: chr6-111913070; COSMIC: COSV60675422; COSMIC: COSV60675422;