rs7027246

Variant names:

• chr9-136917133-A-G
• rs7027246
• NM_021138.4:c.678+518A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021138.4(TRAF2):​c.678+518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,156 control chromosomes in the GnomAD database, including 47,141 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 0.78 (47141 hom., cov: 32)
• Consequence: TRAF2 NM_021138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021138.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF2	NM_021138.4	MANE Select	c.678+518A>G		intron	N/A	NP_066961.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF2	ENST00000247668.7	TSL:1 MANE Select	c.678+518A>G		intron	N/A	ENSP00000247668.2	Q12933-1
	TRAF2	ENST00000882556.1		c.834+518A>G		intron	N/A	ENSP00000552615.1
	TRAF2	ENST00000882557.1		c.678+518A>G		intron	N/A	ENSP00000552616.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119091 AN: 152038 Hom.: 47103 Cov.: 32

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.783 AC: 119187 AN: 152156 Hom.: 47141 Cov.: 32 AF XY: 0.782 AC XY: 58172 AN XY: 74386

African (AFR) AF: 0.892 AC: 37041 AN: 41532

American (AMR) AF: 0.655 AC: 10016 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2714 AN: 3470

East Asian (EAS) AF: 0.870 AC: 4501 AN: 5176

South Asian (SAS) AF: 0.826 AC: 3978 AN: 4816

European-Finnish (FIN) AF: 0.723 AC: 7646 AN: 10582

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.747 AC: 50760 AN: 67980

Other (OTH) AF: 0.756 AC: 1597 AN: 2112

Alfa AF: 0.784 Hom.: 6569

Bravo AF: 0.780

Asia WGS AF: 0.820 AC: 2854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.26
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7027246; hg19: chr9-139811585;