9-120927319-C-T

Variant names:

• chr9-120927319-C-T
• rs3761846
• ENST00000540010.1:c.-365-631G>A

Variant summary

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

The NM_001190945.2(TRAF1):​c.-365-631G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,950 control chromosomes in the GnomAD database, including 21,191 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 0.52 (21189 hom., cov: 31)
  • Exomes 𝑓: 0.50 (2 hom.)
• Consequence: TRAF1 NM_001190945.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 18 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.674 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.-365-631G>A		intron	N/A	NP_001177874.1	Q13077-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF1	ENST00000540010.1	TSL:1	c.-365-631G>A		intron	N/A	ENSP00000443183.1	Q13077-1
	TRAF1	ENST00000871615.1		c.-957G>A		5_prime_UTR	Exon 1 of 8	ENSP00000541674.1
	TRAF1	ENST00000871616.1		c.-365-631G>A		intron	N/A	ENSP00000541675.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79003 AN: 151818 Hom.: 21172 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.683

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.500 AC: 7 AN: 14 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 5 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 3 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.520 AC: 79052 AN: 151936 Hom.: 21189 Cov.: 31 AF XY: 0.526 AC XY: 39053 AN XY: 74254

African (AFR) AF: 0.382 AC: 15844 AN: 41426

American (AMR) AF: 0.596 AC: 9107 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2300 AN: 3468

East Asian (EAS) AF: 0.499 AC: 2577 AN: 5164

South Asian (SAS) AF: 0.694 AC: 3339 AN: 4812

European-Finnish (FIN) AF: 0.542 AC: 5703 AN: 10524

Middle Eastern (MID) AF: 0.676 AC: 196 AN: 290

European-Non Finnish (NFE) AF: 0.565 AC: 38372 AN: 67948

Other (OTH) AF: 0.568 AC: 1199 AN: 2110

Alfa AF: 0.514 Hom.: 3488

Bravo AF: 0.517

Asia WGS AF: 0.582 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.59
PhyloP100		0.094
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: rs3761846; hg19: chr9-123689597; COSMIC: COSV65868023;