rs12147254

Positions:

• chr14-102799329-G-A
• chr14-102799329-G-C

Variant summary

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

The NM_145725.3(TRAF3):​c.-157+21654G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,122 control chromosomes in the GnomAD database, including 5,198 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 0.24 (5198 hom., cov: 32)
• Consequence: TRAF3 NM_145725.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624

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 (SAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF3	NM_145725.3	c.-157+21654G>A		intron_variant		ENST00000392745.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF3	ENST00000392745.8	c.-157+21654G>A		intron_variant		1	NM_145725.3	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35926 AN: 152004 Hom.: 5207 Cov.: 32

Gnomad AFR AF: 0.0772

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.236 AC: 35905 AN: 152122 Hom.: 5198 Cov.: 32 AF XY: 0.238 AC XY: 17676 AN XY: 74370

Gnomad4 AFR AF: 0.0771

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.261

Alfa AF: 0.288 Hom.: 10316

Bravo AF: 0.222

Asia WGS AF: 0.382 AC: 1330 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	0.71
DANN	Benign	0.73

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: rs12147254; hg19: chr14-103265666;