dbSNP rs3750512: TRAF2:c.*715G>A (chr9-136926616-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000850853.1(TRAF2):c.*715G>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 0.629 in 156,638 control chromosomes in the GnomAD database, including 31,299 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 0.63 ( 30462 hom., cov: 34)

Exomes 𝑓: 0.59 ( 837 hom. )

Consequence

TRAF2
ENST00000850853.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

16 publications found

Variant links:

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]

TRAF2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF2	NM_021138.4 link	c.*715G>A		downstream_gene_variant		ENST00000247668.7	NP_066961.2	Q12933-1A0A024R8H5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF2	ENST00000850853.1 link	c.*715G>A		3_prime_UTR_variant	Exon 11 of 11			ENSP00000520942.1
TRAF2	ENST00000247668.7 link	c.*715G>A		downstream_gene_variant		1	NM_021138.4	ENSP00000247668.2		Q12933-1

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95790

AN:

152074

Hom.:

30448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.624

Gnomad AMI

AF:

0.641

Gnomad AMR

AF:

0.537

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.849

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.622

Gnomad OTH

AF:

0.636

GnomAD4 exome

AF:

0.591

AC:

2628

AN:

4446

Hom.:

837

Cov.:

AF XY:

0.597

AC XY:

1362

AN XY:

2282

show subpopulations

African (AFR)

AF:

0.846

AC:

AN:

American (AMR)

AF:

0.489

AC:

639

AN:

1308

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

AN:

East Asian (EAS)

AF:

0.730

AC:

143

AN:

196

South Asian (SAS)

AF:

0.743

AC:

226

AN:

304

European-Finnish (FIN)

AF:

0.571

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.611

AC:

1463

AN:

2394

Other (OTH)

AF:

0.632

AC:

120

AN:

190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

142

189

236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.630

AC:

95857

AN:

152192

Hom.:

30462

Cov.:

AF XY:

0.634

AC XY:

47181

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.623

AC:

25886

AN:

41528

American (AMR)

AF:

0.538

AC:

8219

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.671

AC:

2330

AN:

3472

East Asian (EAS)

AF:

0.849

AC:

4392

AN:

5174

South Asian (SAS)

AF:

0.749

AC:

3617

AN:

4832

European-Finnish (FIN)

AF:

0.658

AC:

6975

AN:

10602

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.622

AC:

42313

AN:

67976

Other (OTH)

AF:

0.641

AC:

1356

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1876

3752

5628

7504

9380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.622

Hom.:

93068

Bravo

AF:

0.616

Asia WGS

AF:

0.766

AC:

2661

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.7

(source)

DANN

Benign

0.62

PhyloP100

-0.058

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over