9-136899648-C-T

Variant names:

• chr9-136899648-C-T
• rs148192660
• NM_021138.4:c.243C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_021138.4(TRAF2):​c.243C>T​(p.Gly81Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,612,882 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (9 hom.)
• Consequence: TRAF2 NM_021138.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.187
• Publications: 3 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 9-136899648-C-T is Benign according to our data. Variant chr9-136899648-C-T is described in ClinVar as Benign. ClinVar VariationId is 719349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.187 with no splicing effect.
• BS2: High AC in GnomAd4 at 296 AD gene.

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.243C>T	p.Gly81Gly	synonymous	Exon 3 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.243C>T	p.Gly81Gly	synonymous	Exon 3 of 11	ENSP00000247668.2	Q12933-1
	TRAF2	ENST00000882556.1		c.243C>T	p.Gly81Gly	synonymous	Exon 3 of 11	ENSP00000552615.1
	TRAF2	ENST00000882557.1		c.243C>T	p.Gly81Gly	synonymous	Exon 3 of 11	ENSP00000552616.1

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 296 AN: 152154 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00351

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00224 AC: 562 AN: 251396 AF XY: 0.00217

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000761

Gnomad FIN exome AF: 0.00171

Gnomad NFE exome AF: 0.00388

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00314 AC: 4592 AN: 1460610 Hom.: 9 Cov.: 30 AF XY: 0.00305 AC XY: 2216 AN XY: 726540

African (AFR) AF: 0.000598 AC: 20 AN: 33444

American (AMR) AF: 0.000537 AC: 24 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26108

East Asian (EAS) AF: 0.000858 AC: 34 AN: 39650

South Asian (SAS) AF: 0.00115 AC: 99 AN: 86212

European-Finnish (FIN) AF: 0.00210 AC: 112 AN: 53330

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.00374 AC: 4150 AN: 1111086

Other (OTH) AF: 0.00247 AC: 149 AN: 60330

GnomAD4 genome AF: 0.00194 AC: 296 AN: 152272 Hom.: 0 Cov.: 33 AF XY: 0.00158 AC XY: 118 AN XY: 74456

African (AFR) AF: 0.000481 AC: 20 AN: 41554

American (AMR) AF: 0.000589 AC: 9 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00351 AC: 239 AN: 68018

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00291 Hom.: 0

Bravo AF: 0.00195

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.7
DANN	Benign	0.87
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs148192660; hg19: chr9-139794100;