rs2269059

Positions:

• chr9-120920194-T-A
• chr9-120920194-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF1	NM_005658.5	c.228+3511A>T		intron_variant		ENST00000373887.8	NP_005649.1
TRAF1	NM_001190945.2	c.228+3511A>T		intron_variant			NP_001177874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF1	ENST00000373887.8	c.228+3511A>T		intron_variant		1	NM_005658.5	ENSP00000362994.3
TRAF1	ENST00000540010.1	c.228+3511A>T		intron_variant		1		ENSP00000443183.1

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

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.0968

Gnomad4 ASJ AF: 0.0813

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.0793

Gnomad4 OTH AF: 0.120

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.5
DANN	Benign	0.81

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: rs2269059; hg19: chr9-123682472;