rs12148050

Variant names:

• chr14-102797451-A-G
• rs12148050
• NM_145725.3:c.-157+19776A>G

Variant summary

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

The NM_145725.3(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 NM_145725.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• Publications: 22 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 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.-157+19776A>G		intron	N/A	NP_663777.1	Q13114-1
	TRAF3	NM_003300.4		c.-18+19776A>G		intron	N/A	NP_003291.2
	TRAF3	NM_145726.3		c.-157+19776A>G		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.-157+19776A>G		intron	N/A	ENSP00000376500.3	Q13114-1
	TRAF3	ENST00000560371.5	TSL:1	c.-18+19776A>G		intron	N/A	ENSP00000454207.1	Q13114-1
	TRAF3	ENST00000351691.10	TSL:1	c.-157+19776A>G		intron	N/A	ENSP00000332468.5	A6NHG8

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

African (AFR) AF: 0.225 AC: 9314 AN: 41446

American (AMR) AF: 0.451 AC: 6879 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2228 AN: 3472

East Asian (EAS) AF: 0.567 AC: 2922 AN: 5152

South Asian (SAS) AF: 0.741 AC: 3563 AN: 4810

European-Finnish (FIN) AF: 0.621 AC: 6550 AN: 10556

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

European-Non Finnish (NFE) AF: 0.653 AC: 44359 AN: 67930

Other (OTH) AF: 0.543 AC: 1147 AN: 2112

Alfa AF: 0.613 Hom.: 52026

Bravo AF: 0.484

Asia WGS AF: 0.627 AC: 2182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		-0.30
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: rs12148050; hg19: chr14-103263788;