rs567455701

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000392745.8(TRAF3):c.245+8_245+19delCCCTCGCCCGGC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,612,482 control chromosomes in the GnomAD database, including 18 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 8 hom. )

Consequence

TRAF3
ENST00000392745.8 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.744

Publications

0 publications found

Variant links:

Genes affected

TRAF3 (HGNC:12033): (TNF receptor associated factor 3) The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from, members of the TNF receptor (TNFR) superfamily. This protein participates in the signal transduction of CD40, a TNFR family member important for the activation of the immune response. This protein is found to be a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex, which induces NF-kappaB activation and cell death initiated by LTbeta ligation. Epstein-Barr virus encoded latent infection membrane protein-1 (LMP1) can interact with this and several other members of the TRAF family, which may be essential for the oncogenic effects of LMP1. The protein also plays a role in the regulation of antiviral response. Mutations in this are associated with Encephalopathy, acute, infection-induced, herpes-specific 5. [provided by RefSeq, Jul 2020]

TRAF3 Gene-Disease associations (from GenCC):

herpes simplex encephalitis, susceptibility to, 3
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
TRAF3 haploinsufficiency
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

TRAF3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 14-102870453-GCCCTCGCCCGGC-G is Benign according to our data. Variant chr14-102870453-GCCCTCGCCCGGC-G is described in ClinVar as Benign. ClinVar VariationId is 473290.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00538 (820/152326) while in subpopulation AFR AF = 0.019 (788/41566). AF 95% confidence interval is 0.0179. There are 10 homozygotes in GnomAd4. There are 377 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 820 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392745.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRAF3	NM_145725.3	MANE Select	c.245+10_245+21delCTCGCCCGGCCC	intron	N/A	NP_663777.1	Q13114-1
TRAF3	NM_003300.4		c.245+10_245+21delCTCGCCCGGCCC	intron	N/A	NP_003291.2
TRAF3	NM_145726.3		c.245+10_245+21delCTCGCCCGGCCC	intron	N/A	NP_663778.1	A6NHG8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRAF3	ENST00000392745.8	TSL:1 MANE Select	c.245+8_245+19delCCCTCGCCCGGC	splice_region intron	N/A	ENSP00000376500.3	Q13114-1
TRAF3	ENST00000560371.5	TSL:1	c.245+8_245+19delCCCTCGCCCGGC	splice_region intron	N/A	ENSP00000454207.1	Q13114-1
TRAF3	ENST00000351691.10	TSL:1	c.245+8_245+19delCCCTCGCCCGGC	splice_region intron	N/A	ENSP00000332468.5	A6NHG8

Frequencies

GnomAD3 genomes

AF:

0.00537

AC:

818

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0190

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00142

AC:

349

AN:

245754

AF XY:

0.000929

show subpopulations

Gnomad AFR exome

AF:

0.0187

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000456

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000560

AC:

817

AN:

1460156

Hom.:

AF XY:

0.000465

AC XY:

338

AN XY:

726356

show subpopulations

African (AFR)

AF:

0.0197

AC:

659

AN:

33438

American (AMR)

AF:

0.00146

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53180

Middle Eastern (MID)

AF:

0.000398

AC:

AN:

5026

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1111684

Other (OTH)

AF:

0.00113

AC:

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00538

AC:

820

AN:

152326

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

377

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0190

AC:

788

AN:

41566

American (AMR)

AF:

0.00163

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00313

Hom.:

Bravo

AF:

0.00646

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Herpes simplex encephalitis, susceptibility to, 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.74

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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