9-136925969-G-A

Variant names:

• chr9-136925969-G-A
• rs7852970
• NM_021138.4:c.*68G>A

Variant summary

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

The NM_021138.4(TRAF2):​c.*68G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,573,294 control chromosomes in the GnomAD database, including 278,112 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 0.58 (25706 hom., cov: 34)
  • Exomes 𝑓: 0.59 (252406 hom.)
• Consequence: TRAF2 NM_021138.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.92
• Publications: 24 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 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.*68G>A		3_prime_UTR	Exon 11 of 11	NP_066961.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF2	ENST00000247668.7	TSL:1 MANE Select	c.*68G>A		3_prime_UTR	Exon 11 of 11	ENSP00000247668.2	Q12933-1
	TRAF2	ENST00000882556.1		c.*68G>A		3_prime_UTR	Exon 11 of 11	ENSP00000552615.1
	TRAF2	ENST00000882557.1		c.*68G>A		3_prime_UTR	Exon 11 of 11	ENSP00000552616.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87851 AN: 152010 Hom.: 25699 Cov.: 34

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.586

GnomAD2 exomes AF: 0.590 AC: 138229 AN: 234216 AF XY: 0.601

Gnomad AFR exome AF: 0.518

Gnomad AMR exome AF: 0.417

Gnomad ASJ exome AF: 0.665

Gnomad EAS exome AF: 0.712

Gnomad FIN exome AF: 0.652

Gnomad NFE exome AF: 0.597

Gnomad OTH exome AF: 0.605

GnomAD4 exome AF: 0.593 AC: 843291 AN: 1421166 Hom.: 252406 Cov.: 25 AF XY: 0.597 AC XY: 422903 AN XY: 708676

African (AFR) AF: 0.504 AC: 16455 AN: 32652

American (AMR) AF: 0.429 AC: 18674 AN: 43578

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 17169 AN: 25864

East Asian (EAS) AF: 0.735 AC: 28806 AN: 39190

South Asian (SAS) AF: 0.663 AC: 56353 AN: 84970

European-Finnish (FIN) AF: 0.649 AC: 31825 AN: 49058

Middle Eastern (MID) AF: 0.635 AC: 3617 AN: 5698

European-Non Finnish (NFE) AF: 0.587 AC: 634835 AN: 1081076

Other (OTH) AF: 0.602 AC: 35557 AN: 59080

GnomAD4 genome AF: 0.578 AC: 87891 AN: 152128 Hom.: 25706 Cov.: 34 AF XY: 0.582 AC XY: 43265 AN XY: 74376

African (AFR) AF: 0.513 AC: 21304 AN: 41522

American (AMR) AF: 0.496 AC: 7581 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2294 AN: 3472

East Asian (EAS) AF: 0.709 AC: 3652 AN: 5150

South Asian (SAS) AF: 0.684 AC: 3300 AN: 4826

European-Finnish (FIN) AF: 0.646 AC: 6849 AN: 10600

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40931 AN: 67954

Other (OTH) AF: 0.591 AC: 1251 AN: 2116

Alfa AF: 0.579 Hom.: 21366

Bravo AF: 0.558

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.097
DANN	Benign	0.63
PhyloP100		-3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7852970; hg19: chr9-139820421; COSMIC: COSV56036356; COSMIC: COSV56036356;