chr9-120927961-G-A

Position:

• chr9-120927961-G-A

Variant summary

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

The ENST00000540010.1(TRAF1):​c.-366+1153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,006 control chromosomes in the GnomAD database, including 21,763 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 0.53 (21716 hom., cov: 31)
  • Exomes 𝑓: 0.66 (47 hom.)
• Consequence: TRAF1 ENST00000540010.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF1	NM_001190945.2	c.-366+1153C>T		intron_variant			NP_001177874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF1	ENST00000540010.1	c.-366+1153C>T		intron_variant		1		ENSP00000443183	P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80181 AN: 151694 Hom.: 21701 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.660 AC: 128 AN: 194 Hom.: 47 Cov.: 0 AF XY: 0.638 AC XY: 74 AN XY: 116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.756

Gnomad4 OTH exome AF: 0.656

GnomAD4 genome AF: 0.529 AC: 80233 AN: 151812 Hom.: 21716 Cov.: 31 AF XY: 0.534 AC XY: 39598 AN XY: 74180

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.574

Alfa AF: 0.574 Hom.: 50748

Bravo AF: 0.525

Asia WGS AF: 0.614 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.76

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: rs3761847; hg19: chr9-123690239; COSMIC: COSV65868031;