9-120920194-T-A

Variant names:

• chr9-120920194-T-A
• rs2269059
• NM_005658.5:c.228+3511A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005658.5(TRAF1):​c.228+3511A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,212 control chromosomes in the GnomAD database, including 2,290 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 0.14 (2290 hom., cov: 32)
• Consequence: TRAF1 NM_005658.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005658.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF1	NM_005658.5	MANE Select	c.228+3511A>T		intron	N/A	NP_005649.1
	TRAF1	NM_001190945.2		c.228+3511A>T		intron	N/A	NP_001177874.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF1	ENST00000373887.8	TSL:1 MANE Select	c.228+3511A>T		intron	N/A	ENSP00000362994.3
	TRAF1	ENST00000540010.1	TSL:1	c.228+3511A>T		intron	N/A	ENSP00000443183.1
	TRAF1	ENST00000871615.1		c.228+3511A>T		intron	N/A	ENSP00000541674.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21566 AN: 152094 Hom.: 2277 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.142 AC: 21610 AN: 152212 Hom.: 2290 Cov.: 32 AF XY: 0.137 AC XY: 10210 AN XY: 74442

African (AFR) AF: 0.290 AC: 12035 AN: 41488

American (AMR) AF: 0.0968 AC: 1480 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3468

East Asian (EAS) AF: 0.220 AC: 1139 AN: 5178

South Asian (SAS) AF: 0.123 AC: 595 AN: 4826

European-Finnish (FIN) AF: 0.0345 AC: 366 AN: 10622

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0793 AC: 5393 AN: 68014

Other (OTH) AF: 0.120 AC: 254 AN: 2114

Alfa AF: 0.0497 Hom.: 50

Bravo AF: 0.153

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.5
DANN	Benign	0.81
PhyloP100		0.090
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2269059; hg19: chr9-123682472;