rs2239657

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005658.5(TRAF1):c.1020C>T(p.Pro340Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,613,556 control chromosomes in the GnomAD database, including 362,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36129 hom., cov: 31)

Exomes 𝑓: 0.67 ( 326630 hom. )

Consequence

TRAF1
NM_005658.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.01

Publications

40 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 9-120909242-G-A is Benign according to our data. Variant chr9-120909242-G-A is described in ClinVar as Benign. ClinVar VariationId is 403564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

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
TRAF1	NM_005658.5 link	c.1020C>T	p.Pro340Pro	synonymous_variant	Exon 7 of 8	ENST00000373887.8	NP_005649.1
TRAF1	NM_001190945.2 link	c.1020C>T	p.Pro340Pro	synonymous_variant	Exon 8 of 9		NP_001177874.1
TRAF1	NM_001190947.2 link	c.654C>T	p.Pro218Pro	synonymous_variant	Exon 5 of 6		NP_001177876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
TRAF1	ENST00000373887.8 link	c.1020C>T	p.Pro340Pro	synonymous_variant	Exon 7 of 8	1	NM_005658.5	ENSP00000362994.3
TRAF1	ENST00000540010.1 link	c.1020C>T	p.Pro340Pro	synonymous_variant	Exon 8 of 9	1		ENSP00000443183.1
TRAF1	ENST00000546084.5 link	c.654C>T	p.Pro218Pro	synonymous_variant	Exon 5 of 6	2		ENSP00000438583.1

Frequencies

GnomAD3 genomes

AF:

0.687

AC:

104285

AN:

151860

Hom.:

36083

Cov.:

show subpopulations

Gnomad AFR

AF:

0.756

Gnomad AMI

AF:

0.490

Gnomad AMR

AF:

0.703

Gnomad ASJ

AF:

0.745

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.818

Gnomad FIN

AF:

0.577

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.645

Gnomad OTH

AF:

0.707

GnomAD2 exomes

AF:

0.688

AC:

172859

AN:

251212

AF XY:

0.694

show subpopulations

Gnomad AFR exome

AF:

0.761

Gnomad AMR exome

AF:

0.719

Gnomad ASJ exome

AF:

0.734

Gnomad EAS exome

AF:

0.705

Gnomad FIN exome

AF:

0.564

Gnomad NFE exome

AF:

0.651

Gnomad OTH exome

AF:

0.682

GnomAD4 exome

AF:

0.666

AC:

973581

AN:

1461578

Hom.:

326630

Cov.:

AF XY:

0.671

AC XY:

488185

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.754

AC:

25250

AN:

33478

American (AMR)

AF:

0.722

AC:

32290

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.730

AC:

19082

AN:

26136

East Asian (EAS)

AF:

0.717

AC:

28471

AN:

39690

South Asian (SAS)

AF:

0.821

AC:

70815

AN:

86224

European-Finnish (FIN)

AF:

0.568

AC:

30347

AN:

53408

Middle Eastern (MID)

AF:

0.756

AC:

4266

AN:

5646

European-Non Finnish (NFE)

AF:

0.649

AC:

721609

AN:

1111914

Other (OTH)

AF:

0.687

AC:

41451

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

18589

37177

55766

74354

92943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19042

38084

57126

76168

95210

<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:

0.687

AC:

104381

AN:

151978

Hom.:

36129

Cov.:

AF XY:

0.687

AC XY:

51043

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.756

AC:

31346

AN:

41476

American (AMR)

AF:

0.704

AC:

10733

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.745

AC:

2582

AN:

3468

East Asian (EAS)

AF:

0.720

AC:

3712

AN:

5158

South Asian (SAS)

AF:

0.818

AC:

3943

AN:

4820

European-Finnish (FIN)

AF:

0.577

AC:

6090

AN:

10552

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.645

AC:

43810

AN:

67942

Other (OTH)

AF:

0.706

AC:

1485

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1660

3320

4980

6640

8300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<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:

0.674

Hom.:

52793

Bravo

AF:

0.697

Asia WGS

AF:

0.773

AC:

2685

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.0

(source)

DANN

Benign

0.65

PhyloP100

-1.0

Mutation Taster

=92/8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over