9-120927319-C-T

Position:

• chr9-120927319-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001190945.2(TRAF1):​c.-365-631G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,950 control chromosomes in the GnomAD database, including 21,191 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (21189 hom., cov: 31)
  • Exomes 𝑓: 0.50 (2 hom.)
• Consequence: TRAF1 NM_001190945.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF1	NM_001190945.2	c.-365-631G>A		intron_variant			NP_001177874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF1	ENST00000540010.1	c.-365-631G>A		intron_variant		1		ENSP00000443183.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79003 AN: 151818 Hom.: 21172 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.683

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.500 AC: 7 AN: 14 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 5 AN XY: 10

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.375

GnomAD4 genome AF: 0.520 AC: 79052 AN: 151936 Hom.: 21189 Cov.: 31 AF XY: 0.526 AC XY: 39053 AN XY: 74254

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.568

Alfa AF: 0.518 Hom.: 3428

Bravo AF: 0.517

Asia WGS AF: 0.582 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.59

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: rs3761846; hg19: chr9-123689597; COSMIC: COSV65868023;