rs11160707

Positions:

• chr14-102908373-G-A
• chr14-102908373-G-T

Variant summary

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

The NM_145725.3(TRAF3):​c.*2589G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 152,688 control chromosomes in the GnomAD database, including 156 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 0.019 (156 hom., cov: 34)
  • Exomes 𝑓: 0.0034 (0 hom.)
• Consequence: TRAF3 NM_145725.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

Genes affected

TRAF3 (HGNC:12033): (TNF receptor associated factor 3) The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from, members of the TNF receptor (TNFR) superfamily. This protein participates in the signal transduction of CD40, a TNFR family member important for the activation of the immune response. This protein is found to be a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex, which induces NF-kappaB activation and cell death initiated by LTbeta ligation. Epstein-Barr virus encoded latent infection membrane protein-1 (LMP1) can interact with this and several other members of the TRAF family, which may be essential for the oncogenic effects of LMP1. The protein also plays a role in the regulation of antiviral response. Mutations in this are associated with Encephalopathy, acute, infection-induced, herpes-specific 5. [provided by RefSeq, Jul 2020]

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 (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3	NM_145725.3	c.*2589G>A		3_prime_UTR_variant	12/12	ENST00000392745.8	NP_663777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3	ENST00000392745.8	c.*2589G>A		3_prime_UTR_variant	12/12	1	NM_145725.3	ENSP00000376500	P1

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2878 AN: 152274 Hom.: 154 Cov.: 34

Gnomad AFR AF: 0.00393

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00347

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.00338 AC: 1 AN: 296 Hom.: 0 Cov.: 0 AF XY: 0.00450 AC XY: 1 AN XY: 222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0625

GnomAD4 genome AF: 0.0190 AC: 2893 AN: 152392 Hom.: 156 Cov.: 34 AF XY: 0.0209 AC XY: 1554 AN XY: 74518

Gnomad4 AFR AF: 0.00392

Gnomad4 AMR AF: 0.0923

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0240

Gnomad4 FIN AF: 0.0154

Gnomad4 NFE AF: 0.00347

Gnomad4 OTH AF: 0.0236

Alfa AF: 0.0140 Hom.: 34

Bravo AF: 0.0280

Asia WGS AF: 0.0830 AC: 286 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	1.1
DANN	Benign	0.82

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: rs11160707; hg19: chr14-103374710;