Genetic Variant TRAF1:c.-365-631G>A (chr9-120927319-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001190945.2(TRAF1):c.-365-631G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,950 control chromosomes in the GnomAD database, including 21,191 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 0.52 ( 21189 hom., cov: 31)

Exomes 𝑓: 0.50 ( 2 hom. )

Consequence

TRAF1
NM_001190945.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940

Publications

18 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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190945.2. 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
	TRAF1	NM_001190945.2		c.-365-631G>A		intron	N/A	NP_001177874.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TRAF1	ENST00000540010.1	TSL:1	c.-365-631G>A	intron	N/A	ENSP00000443183.1
TRAF1	ENST00000871615.1		c.-957G>A	5_prime_UTR	Exon 1 of 8	ENSP00000541674.1
TRAF1	ENST00000871616.1		c.-365-631G>A	intron	N/A	ENSP00000541675.1

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

79003

AN:

151818

Hom.:

21172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.595

Gnomad ASJ

AF:

0.663

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.692

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.683

Gnomad NFE

AF:

0.565

Gnomad OTH

AF:

0.568

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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:

0.520

AC:

79052

AN:

151936

Hom.:

21189

Cov.:

AF XY:

0.526

AC XY:

39053

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.382

AC:

15844

AN:

41426

American (AMR)

AF:

0.596

AC:

9107

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.663

AC:

2300

AN:

3468

East Asian (EAS)

AF:

0.499

AC:

2577

AN:

5164

South Asian (SAS)

AF:

0.694

AC:

3339

AN:

4812

European-Finnish (FIN)

AF:

0.542

AC:

5703

AN:

10524

Middle Eastern (MID)

AF:

0.676

AC:

196

AN:

290

European-Non Finnish (NFE)

AF:

0.565

AC:

38372

AN:

67948

Other (OTH)

AF:

0.568

AC:

1199

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1884

3767

5651

7534

9418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.514

Hom.:

3488

Bravo

AF:

0.517

Asia WGS

AF:

0.582

AC:

2022

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.5

(source)

DANN

Benign

0.59

PhyloP100

0.094

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