rs2416804

chr9-120914118-G-Cchr9-120914118-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005658.5(TRAF1):c.294+117C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 873,232 control chromosomes in the GnomAD database, including 135,158 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 0.46 (18336 hom., cov: 31)
  • Exomes 𝑓: 0.56 (116822 hom.)
• Consequence: TRAF1 NM_005658.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF1	NM_005658.5	c.294+117C>G		intron_variant		ENST00000373887.8
TRAF1	NM_001190945.2	c.294+117C>G		intron_variant
TRAF1	NM_001190947.2	c.-73+117C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF1	ENST00000373887.8	c.294+117C>G		intron_variant		1	NM_005658.5	P1
TRAF1	ENST00000540010.1	c.294+117C>G		intron_variant		1		P1
TRAF1	ENST00000546084.5	c.-73+117C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69395 AN: 151850 Hom.: 18324 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.563 AC: 406352 AN: 721264 Hom.: 116822 AF XY: 0.567 AC XY: 202992 AN XY: 358188

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.648

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 0.527

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.554

GnomAD4 genome AF: 0.457 AC: 69428 AN: 151968 Hom.: 18336 Cov.: 31 AF XY: 0.464 AC XY: 34438 AN XY: 74268

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.523

Alfa AF: 0.349 Hom.: 973

Bravo AF: 0.445

Asia WGS AF: 0.563 AC: 1956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.3
Dann	Benign	0.41

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: rs2416804; hg19: chr9-123676396; COSMIC: COSV65867993;