dbSNP rs567455701: TRAF3:c.245+10_245+21delCTCGCCCGGCCC (chr14-102870453-GCCCTCGCCCGGC-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -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. 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 820 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3	NM_145725.3 link	c.245+10_245+21delCTCGCCCGGCCC		intron_variant	Intron 3 of 11	ENST00000392745.8	NP_663777.1	Q13114-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF3	ENST00000392745.8 link	c.245+8_245+19delCCCTCGCCCGGC		splice_region_variant, intron_variant	Intron 3 of 11	1	NM_145725.3	ENSP00000376500.3		Q13114-1

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

GnomAD3 exomes

AF:

0.00142

AC:

349

AN:

245754

Hom.:

AF XY:

0.000929

AC XY:

124

AN XY:

133438

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 SAS 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

Gnomad4 AFR exome

AF:

0.0197

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00538

AC:

820

AN:

152326

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

377

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0190

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00313

Hom.:

Bravo

AF:

0.00646

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 3

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over