rs7021880

Variant names:

• chr9-120911612-G-C
• rs7021880
• NM_005658.5:c.706-99C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005658.5(TRAF1):​c.706-99C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,414,608 control chromosomes in the GnomAD database, including 68,434 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 0.27 (6098 hom., cov: 32)
  • Exomes 𝑓: 0.31 (62336 hom.)
• Consequence: TRAF1 NM_005658.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 21 publications found

Genes affected

TRAF1 (HGNC:12031): (TNF receptor associated factor 1) The protein encoded by this gene is a member of the TNF receptor (TNFR) associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from various receptors of the TNFR superfamily. This protein and TRAF2 form a heterodimeric complex, which is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF2 also interacts with inhibitor-of-apoptosis proteins (IAPs), and thus mediates the anti-apoptotic signals from TNF receptors. The expression of this protein can be induced by Epstein-Barr virus (EBV). EBV infection membrane protein 1 (LMP1) is found to interact with this and other TRAF proteins; this interaction is thought to link LMP1-mediated B lymphocyte transformation to the signal transduction from TNFR family receptors. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005658.5. 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
	TRAF1	NM_005658.5	MANE Select	c.706-99C>G		intron	N/A	NP_005649.1	Q13077-1
	TRAF1	NM_001190945.2		c.706-99C>G		intron	N/A	NP_001177874.1	Q13077-1
	TRAF1	NM_001190947.2		c.340-99C>G		intron	N/A	NP_001177876.1	Q13077-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF1	ENST00000373887.8	TSL:1 MANE Select	c.706-99C>G		intron	N/A	ENSP00000362994.3	Q13077-1
	TRAF1	ENST00000540010.1	TSL:1	c.706-99C>G		intron	N/A	ENSP00000443183.1	Q13077-1
	TRAF1	ENST00000871615.1		c.706-99C>G		intron	N/A	ENSP00000541674.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41730 AN: 151950 Hom.: 6092 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.312 AC: 393544 AN: 1262542 Hom.: 62336 AF XY: 0.306 AC XY: 190669 AN XY: 622794

African (AFR) AF: 0.189 AC: 5516 AN: 29196

American (AMR) AF: 0.264 AC: 9511 AN: 35976

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 4667 AN: 20792

East Asian (EAS) AF: 0.283 AC: 10757 AN: 37946

South Asian (SAS) AF: 0.163 AC: 11665 AN: 71656

European-Finnish (FIN) AF: 0.380 AC: 14439 AN: 37950

Middle Eastern (MID) AF: 0.199 AC: 760 AN: 3828

European-Non Finnish (NFE) AF: 0.330 AC: 320936 AN: 972032

Other (OTH) AF: 0.288 AC: 15293 AN: 53166

GnomAD4 genome AF: 0.275 AC: 41748 AN: 152066 Hom.: 6098 Cov.: 32 AF XY: 0.274 AC XY: 20333 AN XY: 74324

African (AFR) AF: 0.189 AC: 7843 AN: 41504

American (AMR) AF: 0.276 AC: 4213 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3468

East Asian (EAS) AF: 0.282 AC: 1456 AN: 5170

South Asian (SAS) AF: 0.168 AC: 808 AN: 4822

European-Finnish (FIN) AF: 0.369 AC: 3897 AN: 10550

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.320 AC: 21771 AN: 67958

Other (OTH) AF: 0.253 AC: 532 AN: 2106

Alfa AF: 0.284 Hom.: 857

Bravo AF: 0.267

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.42
PhyloP100		-0.34
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: rs7021880; hg19: chr9-123673890; COSMIC: COSV107491367;