rs2416804

Variant names:

• chr9-120914118-G-C
• rs2416804
• NM_005658.5:c.294+117C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-120914118-G-C
• chr9-120914118-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 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=-0.83).
• 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 rank	MANE	Protein	UniProt
TRAF1	NM_005658.5	c.294+117C>G		intron_variant	Intron 4 of 7	ENST00000373887.8	NP_005649.1
TRAF1	NM_001190945.2	c.294+117C>G		intron_variant	Intron 5 of 8		NP_001177874.1
TRAF1	NM_001190947.2	c.-73+117C>G		intron_variant	Intron 2 of 5		NP_001177876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF1	ENST00000373887.8	c.294+117C>G		intron_variant	Intron 4 of 7	1	NM_005658.5	ENSP00000362994.3
TRAF1	ENST00000540010.1	c.294+117C>G		intron_variant	Intron 5 of 8	1		ENSP00000443183.1
TRAF1	ENST00000546084.5	c.-73+117C>G		intron_variant	Intron 2 of 5	2		ENSP00000438583.1

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

African (AFR) AF: 0.164 AC: 2895 AN: 17672

American (AMR) AF: 0.602 AC: 10177 AN: 16904

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 8671 AN: 13386

East Asian (EAS) AF: 0.475 AC: 14743 AN: 31048

South Asian (SAS) AF: 0.700 AC: 18545 AN: 26510

European-Finnish (FIN) AF: 0.527 AC: 20439 AN: 38790

Middle Eastern (MID) AF: 0.641 AC: 2462 AN: 3838

European-Non Finnish (NFE) AF: 0.574 AC: 310209 AN: 540230

Other (OTH) AF: 0.554 AC: 18211 AN: 32886

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

African (AFR) AF: 0.171 AC: 7070 AN: 41464

American (AMR) AF: 0.565 AC: 8630 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2300 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2565 AN: 5160

South Asian (SAS) AF: 0.695 AC: 3351 AN: 4820

European-Finnish (FIN) AF: 0.549 AC: 5787 AN: 10548

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38041 AN: 67926

Other (OTH) AF: 0.523 AC: 1103 AN: 2110

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
PhyloP100		0.58
PromoterAI		-0.020	Neutral
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: rs2416804; hg19: chr9-123676396; COSMIC: COSV65867993;