rs142054894

Variant names:

• chr6-111591982-A-AGGT
• rs142054894
• NM_147686.4:c.102_104dupACC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.74
• Publications: 2 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 -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

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.102_104dupACC	p.Pro35dup	disruptive_inframe_insertion	Exon 2 of 9	NP_679211.2	O43734-2
	TRAF3IP2	NM_147200.3		c.129_131dupACC	p.Pro44dup	disruptive_inframe_insertion	Exon 3 of 10	NP_671733.2	O43734-1
	TRAF3IP2	NM_001164281.3		c.102_104dupACC	p.Pro35dup	disruptive_inframe_insertion	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.102_104dupACC	p.Pro35dup	disruptive_inframe_insertion	Exon 2 of 9	ENSP00000357750.5	O43734-2
	TRAF3IP2	ENST00000340026.10	TSL:1	c.129_131dupACC	p.Pro44dup	disruptive_inframe_insertion	Exon 3 of 10	ENSP00000345984.6	O43734-1
	TRAF3IP2	ENST00000528599.1	TSL:1	n.297_299dupACC		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 383 AN: 152220 Hom.: 3 Cov.: 32

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

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.: 61 Cov.: 31 AF XY: 0.00336 AC XY: 2441 AN XY: 727246

African (AFR) AF: 0.000448 AC: 15 AN: 33480

American (AMR) AF: 0.0218 AC: 974 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00245 AC: 64 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: 1 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00187 AC: 2082 AN: 1112010

Other (OTH) AF: 0.00194 AC: 117 AN: 60394

GnomAD4 genome AF: 0.00250 AC: 381 AN: 152338 Hom.: 3 Cov.: 32 AF XY: 0.00256 AC XY: 191 AN XY: 74494

African (AFR) AF: 0.000577 AC: 24 AN: 41580

American (AMR) AF: 0.00555 AC: 85 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.0222 AC: 115 AN: 5188

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00182 AC: 124 AN: 68030

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00291 Hom.: 1

Bravo AF: 0.00368

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.00213

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Candidiasis, familial, 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7
Mutation Taster		=64/36	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs142054894; hg19: chr6-111913185; COSMIC: COSV107416230; COSMIC: COSV107416230;