rs12435483

Variant names:

• chr14-102865271-C-T
• rs12435483
• NM_145725.3:c.-17-4914C>T

Variant summary

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

The NM_145725.3(TRAF3):​c.-17-4914C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,016 control chromosomes in the GnomAD database, including 2,136 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 0.15 (2136 hom., cov: 32)
• Consequence: TRAF3 NM_145725.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3	NM_145725.3	c.-17-4914C>T		intron_variant	Intron 2 of 11	ENST00000392745.8	NP_663777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF3	ENST00000392745.8	c.-17-4914C>T		intron_variant	Intron 2 of 11	1	NM_145725.3	ENSP00000376500.3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22459 AN: 151898 Hom.: 2137 Cov.: 32

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.148 AC: 22443 AN: 152016 Hom.: 2136 Cov.: 32 AF XY: 0.148 AC XY: 11016 AN XY: 74292

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.168

Alfa AF: 0.182 Hom.: 3564

Bravo AF: 0.140

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.71

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: rs12435483; hg19: chr14-103331608;