9-136893001-C-T

Position:

• chr9-136893001-C-T

Variant summary

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

The NM_021138.4(TRAF2):​c.-28-5712C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,210 control chromosomes in the GnomAD database, including 48,761 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 0.80 (48761 hom., cov: 32)
• Consequence: TRAF2 NM_021138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF2	NM_021138.4	c.-28-5712C>T		intron_variant		ENST00000247668.7	NP_066961.2
TRAF2	XM_011518976.4	c.-28-5712C>T		intron_variant			XP_011517278.1
TRAF2	XM_011518977.3	c.-28-5712C>T		intron_variant			XP_011517279.1
TRAF2	XM_047423829.1	c.-29+2459C>T		intron_variant			XP_047279785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF2	ENST00000247668.7	c.-28-5712C>T		intron_variant		1	NM_021138.4	ENSP00000247668.2
TRAF2	ENST00000429509.5	c.-28-5712C>T		intron_variant		3		ENSP00000406524.1
TRAF2	ENST00000419057.5	c.-28-5712C>T		intron_variant		3		ENSP00000405860.1
TRAF2	ENST00000414589.1	c.-29+2459C>T		intron_variant		3		ENSP00000397653.1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121468 AN: 152092 Hom.: 48738 Cov.: 32

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.799 AC: 121547 AN: 152210 Hom.: 48761 Cov.: 32 AF XY: 0.799 AC XY: 59431 AN XY: 74418

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.779

Alfa AF: 0.779 Hom.: 17717

Bravo AF: 0.788

Asia WGS AF: 0.821 AC: 2857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2811761; hg19: chr9-139787453;