9-120921879-G-A

Variant names:

• chr9-120921879-G-A
• rs7021206
• NM_005658.5:c.228+1826C>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+1826C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 151,986 control chromosomes in the GnomAD database, including 33,538 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 0.66 (33538 hom., cov: 31)
• Consequence: TRAF1 NM_005658.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444
• Publications: 21 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.797 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+1826C>T		intron	N/A	NP_005649.1
	TRAF1	NM_001190945.2		c.228+1826C>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+1826C>T		intron	N/A	ENSP00000362994.3
	TRAF1	ENST00000540010.1	TSL:1	c.228+1826C>T		intron	N/A	ENSP00000443183.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100661 AN: 151868 Hom.: 33495 Cov.: 31

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.663 AC: 100754 AN: 151986 Hom.: 33538 Cov.: 31 AF XY: 0.664 AC XY: 49313 AN XY: 74262

African (AFR) AF: 0.673 AC: 27899 AN: 41434

American (AMR) AF: 0.695 AC: 10611 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2580 AN: 3468

East Asian (EAS) AF: 0.721 AC: 3723 AN: 5162

South Asian (SAS) AF: 0.818 AC: 3942 AN: 4820

European-Finnish (FIN) AF: 0.576 AC: 6082 AN: 10552

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43784 AN: 67962

Other (OTH) AF: 0.691 AC: 1456 AN: 2108

Alfa AF: 0.669 Hom.: 8183

Bravo AF: 0.670

Asia WGS AF: 0.768 AC: 2669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.30
DANN	Benign	0.50
PhyloP100		-0.44
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: rs7021206; hg19: chr9-123684157;