rs4880073

Positions:

• chr9-136922901-G-A
• chr9-136922901-G-C
• chr9-136922901-G-T

Variant summary

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

The NM_021138.4(TRAF2):​c.1139-951G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.44 (14790 hom., cov: 18)
• Consequence: TRAF2 NM_021138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

Genes affected

TRAF2 (HGNC:12032): (TNF receptor associated factor 2) 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 superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF1 interacts with the inhibitor-of-apoptosis proteins (IAPs), and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. BIRC2/c-IAP1, an apoptosis inhibitor possessing ubiquitin ligase activity, can unbiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined. [provided by RefSeq, Jul 2008]

TRAF2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF2	NM_021138.4	c.1139-951G>A		intron_variant		ENST00000247668.7	NP_066961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF2	ENST00000247668.7	c.1139-951G>A		intron_variant		1	NM_021138.4	ENSP00000247668.2
TRAF2	ENST00000466107.1	n.203+408G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.443 AC: 55882 AN: 126018 Hom.: 14791 Cov.: 18

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.443 AC: 55921 AN: 126138 Hom.: 14790 Cov.: 18 AF XY: 0.441 AC XY: 26874 AN XY: 60904

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.421

Alfa AF: 0.400 Hom.: 16930

Asia WGS AF: 0.347 AC: 1129 AN: 3252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.9
DANN	Benign	0.58

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: rs4880073; hg19: chr9-139817353; COSMIC: COSV56041905; COSMIC: COSV56041905;