14-102805688-G-A

Variant names:

• chr14-102805688-G-A
• rs8023164
• NM_145725.3:c.-156-24646G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145725.3(TRAF3):​c.-156-24646G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,048 control chromosomes in the GnomAD database, including 22,804 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 0.52 (22804 hom., cov: 31)
• Consequence: TRAF3 NM_145725.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• Publications: 2 publications found

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]

TRAF3 Gene-Disease associations (from GenCC):

• herpes simplex encephalitis, susceptibility to, 3

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• TRAF3 haploinsufficiency

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145725.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3	NM_145725.3	MANE Select	c.-156-24646G>A		intron	N/A	NP_663777.1	Q13114-1
	TRAF3	NM_003300.4		c.-18+28013G>A		intron	N/A	NP_003291.2
	TRAF3	NM_145726.3		c.-156-24646G>A		intron	N/A	NP_663778.1	A6NHG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3	ENST00000392745.8	TSL:1 MANE Select	c.-156-24646G>A		intron	N/A	ENSP00000376500.3	Q13114-1
	TRAF3	ENST00000560371.5	TSL:1	c.-18+28013G>A		intron	N/A	ENSP00000454207.1	Q13114-1
	TRAF3	ENST00000351691.10	TSL:1	c.-156-24646G>A		intron	N/A	ENSP00000332468.5	A6NHG8

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78736 AN: 151930 Hom.: 22814 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.518 AC: 78727 AN: 152048 Hom.: 22804 Cov.: 31 AF XY: 0.521 AC XY: 38697 AN XY: 74320

African (AFR) AF: 0.249 AC: 10330 AN: 41466

American (AMR) AF: 0.453 AC: 6917 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2226 AN: 3470

East Asian (EAS) AF: 0.566 AC: 2926 AN: 5166

South Asian (SAS) AF: 0.739 AC: 3568 AN: 4828

European-Finnish (FIN) AF: 0.621 AC: 6558 AN: 10568

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44291 AN: 67962

Other (OTH) AF: 0.548 AC: 1154 AN: 2106

Alfa AF: 0.448 Hom.: 1937

Bravo AF: 0.491

Asia WGS AF: 0.625 AC: 2174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8023164; hg19: chr14-103272025; COSMIC: COSV61672993;