rs567455701

Positions:

• chr14-102870453-GCCCTCGCCCGGC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_145725.3(TRAF3):​c.245+10_245+21del 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 NM_145725.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.744

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]

ACMG classification

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/exons	MANE	UniProt
TRAF3	NM_145725.3	c.245+10_245+21del		splice_region_variant, intron_variant		ENST00000392745.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF3	ENST00000392745.8	c.245+10_245+21del		splice_region_variant, intron_variant		1	NM_145725.3	P1

Frequencies

GnomAD3 genomes AF: 0.00537 AC: 818 AN: 152208 Hom.: 10 Cov.: 32

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.: 5 AF XY: 0.000929 AC XY: 124 AN XY: 133438

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.: 8 AF XY: 0.000465 AC XY: 338 AN XY: 726356

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.: 10 Cov.: 32 AF XY: 0.00506 AC XY: 377 AN XY: 74484

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.: 0

Bravo AF: 0.00646

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs567455701; hg19: chr14-103336790;