9-136893001-C-A

Position:

• chr9-136893001-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000247668.7(TRAF2):​c.-28-5712C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TRAF2 ENST00000247668.7 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF2	ENST00000247668.7	c.-28-5712C>A		intron_variant		1	NM_021138.4	ENSP00000247668	P1
TRAF2	ENST00000414589.1	c.-29+2459C>A		intron_variant		3		ENSP00000397653
TRAF2	ENST00000419057.5	c.-28-5712C>A		intron_variant		3		ENSP00000405860
TRAF2	ENST00000429509.5	c.-28-5712C>A		intron_variant		3		ENSP00000406524

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.76

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: rs2811761; hg19: chr9-139787453;