rs7021880

Positions:

• chr9-120911612-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF1	NM_005658.5	c.706-99C>G		intron_variant		ENST00000373887.8	NP_005649.1
TRAF1	NM_001190945.2	c.706-99C>G		intron_variant			NP_001177874.1
TRAF1	NM_001190947.2	c.340-99C>G		intron_variant			NP_001177876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF1	ENST00000373887.8	c.706-99C>G		intron_variant		1	NM_005658.5	ENSP00000362994.3
TRAF1	ENST00000540010.1	c.706-99C>G		intron_variant		1		ENSP00000443183.1
TRAF1	ENST00000546084.5	c.340-99C>G		intron_variant		2		ENSP00000438583.1

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

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.283

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.380

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.288

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

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.253

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.42

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: rs7021880; hg19: chr9-123673890;