9-136881948-C-T

Variant names:

• chr9-136881948-C-T
• rs3739942
• ENST00000419057:c.-158C>T

Variant summary

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

The ENST00000419057(TRAF2):​c.-158C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 984,972 control chromosomes in the GnomAD database, including 272,307 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 0.76 (43657 hom., cov: 30)
  • Exomes 𝑓: 0.74 (228650 hom.)
• Consequence: TRAF2 ENST00000419057 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF2	XM_011518976.4	c.-158C>T		upstream_gene_variant			XP_011517278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF2	ENST00000419057	c.-158C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	3		ENSP00000405860.1
TRAF2	ENST00000419057	c.-158C>T		5_prime_UTR_variant	Exon 1 of 6	3		ENSP00000405860.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114898 AN: 151896 Hom.: 43650 Cov.: 30

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.734

GnomAD4 exome AF: 0.741 AC: 616842 AN: 832958 Hom.: 228650 Cov.: 30 AF XY: 0.739 AC XY: 284444 AN XY: 384654

Gnomad4 AFR exome AF: 0.816

Gnomad4 AMR exome AF: 0.585

Gnomad4 ASJ exome AF: 0.773

Gnomad4 EAS exome AF: 0.895

Gnomad4 SAS exome AF: 0.788

Gnomad4 FIN exome AF: 0.752

Gnomad4 NFE exome AF: 0.737

Gnomad4 OTH exome AF: 0.756

GnomAD4 genome AF: 0.756 AC: 114954 AN: 152014 Hom.: 43657 Cov.: 30 AF XY: 0.755 AC XY: 56084 AN XY: 74294

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.738

Alfa AF: 0.749 Hom.: 18229

Bravo AF: 0.752

Asia WGS AF: 0.801 AC: 2785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3739942; hg19: chr9-139776400;