rs12148050

Positions:

• chr14-102797451-A-G

Variant summary

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

The ENST00000392745.8(TRAF3):​c.-157+19776A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,944 control chromosomes in the GnomAD database, including 22,599 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 0.51 (22599 hom., cov: 31)
• Consequence: TRAF3 ENST00000392745.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

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 = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3	NM_145725.3	c.-157+19776A>G		intron_variant		ENST00000392745.8	NP_663777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3	ENST00000392745.8	c.-157+19776A>G		intron_variant		1	NM_145725.3	ENSP00000376500	P1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77719 AN: 151824 Hom.: 22605 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.511 AC: 77719 AN: 151944 Hom.: 22599 Cov.: 31 AF XY: 0.514 AC XY: 38192 AN XY: 74288

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.543

Alfa AF: 0.630 Hom.: 39655

Bravo AF: 0.484

Asia WGS AF: 0.627 AC: 2182 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	1.5
DANN	Benign	0.54

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: rs12148050; hg19: chr14-103263788;