9-120928014-G-C

Variant names:

• chr9-120928014-G-C
• rs2416806
• ENST00000540010.1:c.-366+1100C>G

Variant summary

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

The NM_001190945.2(TRAF1):​c.-366+1100C>G 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 152,062 control chromosomes in the GnomAD database, including 33,572 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 (33553 hom., cov: 31)
  • Exomes 𝑓: 0.64 (19 hom.)
• Consequence: TRAF1 NM_001190945.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 14 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=-0.92).
• 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_001190945.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF1	NM_001190945.2		c.-366+1100C>G		intron	N/A	NP_001177874.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF1	ENST00000540010.1	TSL:1	c.-366+1100C>G		intron	N/A	ENSP00000443183.1
	TRAF1	ENST00000871615.1		c.-1652C>G		5_prime_UTR	Exon 1 of 8	ENSP00000541674.1
	TRAF1	ENST00000871616.1		c.-365-1326C>G		intron	N/A	ENSP00000541675.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100676 AN: 151838 Hom.: 33510 Cov.: 31

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.690

GnomAD4 exome AF: 0.642 AC: 68 AN: 106 Hom.: 19 Cov.: 0 AF XY: 0.694 AC XY: 43 AN XY: 62

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.605 AC: 23 AN: 38

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.717 AC: 33 AN: 46

Other (OTH) AF: 0.600 AC: 12 AN: 20

GnomAD4 genome AF: 0.663 AC: 100769 AN: 151956 Hom.: 33553 Cov.: 31 AF XY: 0.664 AC XY: 49337 AN XY: 74284

African (AFR) AF: 0.674 AC: 27906 AN: 41400

American (AMR) AF: 0.694 AC: 10608 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2581 AN: 3470

East Asian (EAS) AF: 0.721 AC: 3731 AN: 5174

South Asian (SAS) AF: 0.818 AC: 3943 AN: 4818

European-Finnish (FIN) AF: 0.578 AC: 6087 AN: 10530

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

European-Non Finnish (NFE) AF: 0.644 AC: 43779 AN: 67954

Other (OTH) AF: 0.689 AC: 1455 AN: 2112

Alfa AF: 0.648 Hom.: 3778

Bravo AF: 0.670

Asia WGS AF: 0.768 AC: 2671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.73
PhyloP100		-2.6
Mutation Taster		=300/0	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: rs2416806; hg19: chr9-123690292;