9-120917790-G-A

Position:

• chr9-120917790-G-A

Variant summary

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

The NM_005658.5(TRAF1):​c.229-3490C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,370 control chromosomes in the GnomAD database, including 17,859 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 0.45 (17859 hom., cov: 29)
• Consequence: TRAF1 NM_005658.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.687

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=-0.89).
• 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_005658.5	c.229-3490C>T		intron_variant		ENST00000373887.8	NP_005649.1
TRAF1	NM_001190945.2	c.229-3490C>T		intron_variant			NP_001177874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF1	ENST00000373887.8	c.229-3490C>T		intron_variant		1	NM_005658.5	ENSP00000362994	P1
TRAF1	ENST00000540010.1	c.229-3490C>T		intron_variant		1		ENSP00000443183	P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67517 AN: 151252 Hom.: 17847 Cov.: 29

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.516

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.446 AC: 67539 AN: 151370 Hom.: 17859 Cov.: 29 AF XY: 0.452 AC XY: 33416 AN XY: 73890

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.516

Alfa AF: 0.499 Hom.: 3440

Bravo AF: 0.435

Asia WGS AF: 0.559 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.41

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: rs10118357; hg19: chr9-123680068; COSMIC: COSV65868001; COSMIC: COSV65868001;