Genetic Variant ENST00000540010.1:c.-366+1100C>G (chr9-120928014-G-C) – 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+1100C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,062 control chromosomes in the GnomAD database, including 33,572 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 0.66 ( 33553 hom., cov: 31)

Exomes 𝑓: 0.64 ( 19 hom. )

Consequence

TRAF1
ENST00000540010.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.56

Publications

14 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF1	NM_001190945.2 link	c.-366+1100C>G		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+1100C>G		intron_variant	Intron 1 of 8	1		ENSP00000443183.1		Q13077-1

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100676

AN:

151838

Hom.:

33510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.674

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.693

Gnomad ASJ

AF:

0.744

Gnomad EAS

AF:

0.721

Gnomad SAS

AF:

0.818

Gnomad FIN

AF:

0.578

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.690

GnomAD4 exome

AF:

0.642

AC:

AN:

106

Hom.:

Cov.:

AF XY:

0.694

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.605

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.717

AC:

AN:

Other (OTH)

AF:

0.600

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

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:

0.663

AC:

100769

AN:

151956

Hom.:

33553

Cov.:

AF XY:

0.664

AC XY:

49337

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.674

AC:

27906

AN:

41400

American (AMR)

AF:

0.694

AC:

10608

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.744

AC:

2581

AN:

3470

East Asian (EAS)

AF:

0.721

AC:

3731

AN:

5174

South Asian (SAS)

AF:

0.818

AC:

3943

AN:

4818

European-Finnish (FIN)

AF:

0.578

AC:

6087

AN:

10530

Middle Eastern (MID)

AF:

0.796

AC:

234

AN:

294

European-Non Finnish (NFE)

AF:

0.644

AC:

43779

AN:

67954

Other (OTH)

AF:

0.689

AC:

1455

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1756

3512

5268

7024

8780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.648

Hom.:

3778

Bravo

AF:

0.670

Asia WGS

AF:

0.768

AC:

2671

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.20

(source)

DANN

Benign

0.73

PhyloP100

-2.6

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over