rs4880073

Variant names:

• chr9-136922901-G-A
• rs4880073
• NM_021138.4:c.1139-951G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021138.4. 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
	TRAF2	NM_021138.4	MANE Select	c.1139-951G>A		intron	N/A	NP_066961.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF2	ENST00000247668.7	TSL:1 MANE Select	c.1139-951G>A		intron	N/A	ENSP00000247668.2
	TRAF2	ENST00000882556.1		c.1295-951G>A		intron	N/A	ENSP00000552615.1
	TRAF2	ENST00000882557.1		c.1139-855G>A		intron	N/A	ENSP00000552616.1

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

African (AFR) AF: 0.624 AC: 19827 AN: 31794

American (AMR) AF: 0.427 AC: 5466 AN: 12814

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1027 AN: 3120

East Asian (EAS) AF: 0.325 AC: 1387 AN: 4266

South Asian (SAS) AF: 0.454 AC: 1639 AN: 3612

European-Finnish (FIN) AF: 0.353 AC: 3047 AN: 8620

Middle Eastern (MID) AF: 0.292 AC: 76 AN: 260

European-Non Finnish (NFE) AF: 0.381 AC: 22495 AN: 59090

Other (OTH) AF: 0.421 AC: 755 AN: 1794

Alfa AF: 0.424 Hom.: 31746

Asia WGS AF: 0.347 AC: 1129 AN: 3252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.9
DANN	Benign	0.58
PhyloP100		-0.058
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: rs4880073; hg19: chr9-139817353; COSMIC: COSV56041905; COSMIC: COSV56041905;