9-136901052-A-G

Variant names:

• chr9-136901052-A-G
• rs2811757
• NM_021138.4:c.366+532A>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.366+532A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,214 control chromosomes in the GnomAD database, including 48,491 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 (48491 hom., cov: 33)
• Consequence: TRAF2 NM_021138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 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.366+532A>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.366+532A>G		intron	N/A	ENSP00000247668.2	Q12933-1
	TRAF2	ENST00000882556.1		c.522+376A>G		intron	N/A	ENSP00000552615.1
	TRAF2	ENST00000882557.1		c.366+532A>G		intron	N/A	ENSP00000552616.1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 121126 AN: 152094 Hom.: 48468 Cov.: 33

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.796 AC: 121206 AN: 152214 Hom.: 48491 Cov.: 33 AF XY: 0.796 AC XY: 59262 AN XY: 74420

African (AFR) AF: 0.854 AC: 35460 AN: 41512

American (AMR) AF: 0.670 AC: 10233 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2691 AN: 3472

East Asian (EAS) AF: 0.870 AC: 4514 AN: 5190

South Asian (SAS) AF: 0.832 AC: 4013 AN: 4824

European-Finnish (FIN) AF: 0.808 AC: 8561 AN: 10598

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53150 AN: 68016

Other (OTH) AF: 0.777 AC: 1644 AN: 2116

Alfa AF: 0.781 Hom.: 28914

Bravo AF: 0.786

Asia WGS AF: 0.821 AC: 2854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.68
PhyloP100		0.23
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: rs2811757; hg19: chr9-139795504;