rs10781522

chr9-136920601-G-Achr9-136920601-G-C

Variant summary

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

The NM_021138.4(TRAF2):c.960+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,463,100 control chromosomes in the GnomAD database, including 274,169 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 0.59 (27077 hom., cov: 32)
  • Exomes 𝑓: 0.61 (247092 hom.)
• Consequence: TRAF2 NM_021138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF2	NM_021138.4	c.960+86G>A		intron_variant		ENST00000247668.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF2	ENST00000247668.7	c.960+86G>A		intron_variant		1	NM_021138.4	P1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90259 AN: 151896 Hom.: 27076 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.591

GnomAD4 exome AF: 0.612 AC: 801787 AN: 1311088 Hom.: 247092 AF XY: 0.615 AC XY: 393262 AN XY: 639474

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.665

Gnomad4 EAS exome AF: 0.745

Gnomad4 SAS exome AF: 0.726

Gnomad4 FIN exome AF: 0.624

Gnomad4 NFE exome AF: 0.604

Gnomad4 OTH exome AF: 0.617

GnomAD4 genome AF: 0.594 AC: 90288 AN: 152012 Hom.: 27077 Cov.: 32 AF XY: 0.596 AC XY: 44298 AN XY: 74306

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.596

Alfa AF: 0.608 Hom.: 35117

Bravo AF: 0.577

Asia WGS AF: 0.676 AC: 2352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.57
Dann	Benign	0.70

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: rs10781522; hg19: chr9-139815053;