rs7852970

chr9-136925969-G-Achr9-136925969-G-Cchr9-136925969-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.*68G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,573,294 control chromosomes in the GnomAD database, including 278,112 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 0.58 (25706 hom., cov: 34)
  • Exomes 𝑓: 0.59 (252406 hom.)
• Consequence: TRAF2 NM_021138.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.92

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF2	NM_021138.4	c.*68G>A		3_prime_UTR_variant	11/11	ENST00000247668.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF2	ENST00000247668.7	c.*68G>A		3_prime_UTR_variant	11/11	1	NM_021138.4	P1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87851 AN: 152010 Hom.: 25699 Cov.: 34

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.586

GnomAD3 exomes AF: 0.590 AC: 138229 AN: 234216 Hom.: 41534 AF XY: 0.601 AC XY: 76599 AN XY: 127348

Gnomad AFR exome AF: 0.518

Gnomad AMR exome AF: 0.417

Gnomad ASJ exome AF: 0.665

Gnomad EAS exome AF: 0.712

Gnomad SAS exome AF: 0.660

Gnomad FIN exome AF: 0.652

Gnomad NFE exome AF: 0.597

Gnomad OTH exome AF: 0.605

GnomAD4 exome AF: 0.593 AC: 843291 AN: 1421166 Hom.: 252406 Cov.: 25 AF XY: 0.597 AC XY: 422903 AN XY: 708676

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.664

Gnomad4 EAS exome AF: 0.735

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.649

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.602

GnomAD4 genome AF: 0.578 AC: 87891 AN: 152128 Hom.: 25706 Cov.: 34 AF XY: 0.582 AC XY: 43265 AN XY: 74376

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.591

Alfa AF: 0.579 Hom.: 18464

Bravo AF: 0.558

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.097
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7852970; hg19: chr9-139820421; COSMIC: COSV56036356; COSMIC: COSV56036356;