dbSNP rs3761847: 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 NM_001190945.2(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
NM_001190945.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF1	NM_001190945.2 link	c.-366+1153C>T		intron_variant	Intron 1 of 8		NP_001177874.1	Q13077-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF1	ENST00000540010.1 link	c.-366+1153C>T		intron_variant	Intron 1 of 8	1		ENSP00000443183.1		Q13077-1

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

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

Gnomad4 AMR exome

AF:

1.00

AC:

AN:

Gnomad4 ASJ exome

AF:

1.00

AC:

AN:

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

Gnomad4 SAS exome

AF:

0.500

AC:

AN:

Gnomad4 FIN exome

AF:

0.500

AC:

AN:

Gnomad4 NFE exome

AF:

0.756

AC:

AN:

Gnomad4 Remaining exome

AF:

0.656

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.405

AC:

0.404718

AN:

0.404718

Gnomad4 AMR

AF:

0.600

AC:

0.59983

AN:

0.59983

Gnomad4 ASJ

AF:

0.663

AC:

0.663306

AN:

0.663306

Gnomad4 EAS

AF:

0.524

AC:

0.524031

AN:

0.524031

Gnomad4 SAS

AF:

0.702

AC:

0.702381

AN:

0.702381

Gnomad4 FIN

AF:

0.543

AC:

0.542686

AN:

0.542686

Gnomad4 NFE

AF:

0.566

AC:

0.565685

AN:

0.565685

Gnomad4 OTH

AF:

0.574

AC:

0.574478

AN:

0.574478

Heterozygous variant carriers

1911

3822

5733

7644

9555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.7

DANN

Benign

0.76

Mutation Taster

=300/0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over