9-136898474-T-C

Variant names:

• chr9-136898474-T-C
• rs2784075
• NM_021138.4:c.-28-239T>C

Variant summary

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

The NM_021138.4(TRAF2):​c.-28-239T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 590,252 control chromosomes in the GnomAD database, including 183,936 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 (48358 hom., cov: 31)
  • Exomes 𝑓: 0.79 (135578 hom.)
• Consequence: TRAF2 NM_021138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF2	NM_021138.4	MANE Select	c.-28-239T>C		intron	N/A	NP_066961.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF2	ENST00000247668.7	TSL:1 MANE Select	c.-28-239T>C		intron	N/A	ENSP00000247668.2
	TRAF2	ENST00000850853.1		c.-28-239T>C		intron	N/A	ENSP00000520942.1
	TRAF2	ENST00000429509.5	TSL:3	c.-28-239T>C		intron	N/A	ENSP00000406524.1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120908 AN: 151976 Hom.: 48335 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.771

GnomAD4 exome AF: 0.785 AC: 344145 AN: 438158 Hom.: 135578 Cov.: 6 AF XY: 0.784 AC XY: 161248 AN XY: 205722

African (AFR) AF: 0.865 AC: 7024 AN: 8116

American (AMR) AF: 0.585 AC: 276 AN: 472

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2110 AN: 2678

East Asian (EAS) AF: 0.904 AC: 1711 AN: 1892

South Asian (SAS) AF: 0.828 AC: 7113 AN: 8594

European-Finnish (FIN) AF: 0.845 AC: 98 AN: 116

Middle Eastern (MID) AF: 0.755 AC: 664 AN: 880

European-Non Finnish (NFE) AF: 0.782 AC: 313718 AN: 401050

Other (OTH) AF: 0.796 AC: 11431 AN: 14360

GnomAD4 genome AF: 0.795 AC: 120988 AN: 152094 Hom.: 48358 Cov.: 31 AF XY: 0.795 AC XY: 59138 AN XY: 74344

African (AFR) AF: 0.854 AC: 35449 AN: 41508

American (AMR) AF: 0.667 AC: 10181 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2658 AN: 3470

East Asian (EAS) AF: 0.868 AC: 4481 AN: 5160

South Asian (SAS) AF: 0.832 AC: 4007 AN: 4816

European-Finnish (FIN) AF: 0.808 AC: 8557 AN: 10592

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.781 AC: 53086 AN: 67968

Other (OTH) AF: 0.774 AC: 1631 AN: 2106

Alfa AF: 0.776 Hom.: 57572

Bravo AF: 0.785

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	-0.99
CADD	Benign	0.077
DANN	Benign	0.16
PhyloP100		-2.5
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
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: rs2784075; hg19: chr9-139792926;