rs1051743

chr14-102903404-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_145725.3(TRAF3):c.1110C>T(p.Ser370=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,613,988 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (17 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (10 hom.)
• Consequence: TRAF3 NM_145725.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 14-102903404-C-T is Benign according to our data. Variant chr14-102903404-C-T is described in ClinVar as [Benign]. Clinvar id is 473287.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102903404-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.28 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00719 (1094/152194) while in subpopulation AFR AF= 0.0239 (993/41510). AF 95% confidence interval is 0.0227. There are 17 homozygotes in gnomad4. There are 516 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1097 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF3	NM_145725.3	c.1110C>T	p.Ser370=	synonymous_variant	11/12	ENST00000392745.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF3	ENST00000392745.8	c.1110C>T	p.Ser370=	synonymous_variant	11/12	1	NM_145725.3	P1

Frequencies

GnomAD3 genomes AF: 0.00721 AC: 1097 AN: 152076 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00238 AC: 597 AN: 250884 Hom.: 3 AF XY: 0.00198 AC XY: 269 AN XY: 135718

Gnomad AFR exome AF: 0.0247

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00199

Gnomad FIN exome AF: 0.00129

Gnomad NFE exome AF: 0.000274

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000999 AC: 1460 AN: 1461794 Hom.: 10 Cov.: 31 AF XY: 0.000935 AC XY: 680 AN XY: 727200

Gnomad4 AFR exome AF: 0.0240

Gnomad4 AMR exome AF: 0.00224

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00226

Gnomad4 FIN exome AF: 0.00116

Gnomad4 NFE exome AF: 0.000154

Gnomad4 OTH exome AF: 0.00202

GnomAD4 genome AF: 0.00719 AC: 1094 AN: 152194 Hom.: 17 Cov.: 33 AF XY: 0.00693 AC XY: 516 AN XY: 74412

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00329 Hom.: 1

Bravo AF: 0.00787

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000296

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 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	1.1
Dann	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs1051743; hg19: chr14-103369741;