chr14-102910984-G-A

Position:

• chr14-102910984-G-A

Variant summary

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

The NM_145725.3(TRAF3):​c.*5200G>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 0.271 in 152,100 control chromosomes in the GnomAD database, including 6,961 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 (6961 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRAF3 NM_145725.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3	NM_145725.3	c.*5200G>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.*5200G>A		3_prime_UTR_variant	12/12	1	NM_145725.3	ENSP00000376500	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41179 AN: 151982 Hom.: 6936 Cov.: 33

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.240

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.271 AC: 41243 AN: 152100 Hom.: 6961 Cov.: 33 AF XY: 0.271 AC XY: 20137 AN XY: 74336

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.243

Alfa AF: 0.187 Hom.: 5309

Bravo AF: 0.290

Asia WGS AF: 0.254 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.10
DANN	Benign	0.69

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: rs10133111; hg19: chr14-103377321;