Genetic Variant TRAF1:c.-366+1153C>T (chr9-120927961-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 ENST00000540010.1(TRAF1):c.-366+1153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,006 control chromosomes in the GnomAD database, including 21,763 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 0.53 ( 21716 hom., cov: 31)

Exomes 𝑓: 0.66 ( 47 hom. )

Consequence

TRAF1
ENST00000540010.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210

Publications

187 publications found

Variant links:

Genes affected

TRAF1 (HGNC:12031): (TNF receptor associated factor 1) The protein encoded by this gene is a member of the TNF receptor (TNFR) associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from various receptors of the TNFR superfamily. This protein and TRAF2 form a heterodimeric complex, which is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF2 also interacts with inhibitor-of-apoptosis proteins (IAPs), and thus mediates the anti-apoptotic signals from TNF receptors. The expression of this protein can be induced by Epstein-Barr virus (EBV). EBV infection membrane protein 1 (LMP1) is found to interact with this and other TRAF proteins; this interaction is thought to link LMP1-mediated B lymphocyte transformation to the signal transduction from TNFR family receptors. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

TRAF1 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000540010.1. 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
	TRAF1	NM_001190945.2		c.-366+1153C>T		intron	N/A	NP_001177874.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF1	ENST00000540010.1	TSL:1	c.-366+1153C>T		intron	N/A	ENSP00000443183.1

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80181

AN:

151694

Hom.:

21701

Cov.:

show subpopulations

Gnomad AFR

AF:

0.405

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.599

Gnomad ASJ

AF:

0.663

Gnomad EAS

AF:

0.523

Gnomad SAS

AF:

0.701

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.566

Gnomad OTH

AF:

0.574

GnomAD4 exome

AF:

0.660

AC:

128

AN:

194

Hom.:

Cov.:

AF XY:

0.638

AC XY:

AN XY:

116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.756

AC:

AN:

Other (OTH)

AF:

0.656

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.529

AC:

80233

AN:

151812

Hom.:

21716

Cov.:

AF XY:

0.534

AC XY:

39598

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.405

AC:

16727

AN:

41330

American (AMR)

AF:

0.600

AC:

9163

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.663

AC:

2303

AN:

3472

East Asian (EAS)

AF:

0.524

AC:

2704

AN:

5160

South Asian (SAS)

AF:

0.702

AC:

3363

AN:

4788

European-Finnish (FIN)

AF:

0.543

AC:

5721

AN:

10542

Middle Eastern (MID)

AF:

0.677

AC:

199

AN:

294

European-Non Finnish (NFE)

AF:

0.566

AC:

38427

AN:

67930

Other (OTH)

AF:

0.574

AC:

1211

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1911

3822

5733

7644

9555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.564

Hom.:

100940

Bravo

AF:

0.525

Asia WGS

AF:

0.614

AC:

2134

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

1.7

(source)

DANN

Benign

0.76

PhyloP100

-0.021

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over