rs2239657

Variant names:

• chr9-120909242-G-A
• rs2239657
• NM_005658.5:c.1020C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-120909242-G-A
• chr9-120909242-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005658.5(TRAF1):​c.1020C>T​(p.Pro340Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,613,556 control chromosomes in the GnomAD database, including 362,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (36129 hom., cov: 31)
  • Exomes 𝑓: 0.67 (326630 hom.)
• Consequence: TRAF1 NM_005658.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.01
• Publications: 40 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 9-120909242-G-A is Benign according to our data. Variant chr9-120909242-G-A is described in ClinVar as Benign. ClinVar VariationId is 403564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF1	NM_005658.5	MANE Select	c.1020C>T	p.Pro340Pro	synonymous	Exon 7 of 8	NP_005649.1	Q13077-1
	TRAF1	NM_001190945.2		c.1020C>T	p.Pro340Pro	synonymous	Exon 8 of 9	NP_001177874.1	Q13077-1
	TRAF1	NM_001190947.2		c.654C>T	p.Pro218Pro	synonymous	Exon 5 of 6	NP_001177876.1	Q13077-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF1	ENST00000373887.8	TSL:1 MANE Select	c.1020C>T	p.Pro340Pro	synonymous	Exon 7 of 8	ENSP00000362994.3	Q13077-1
	TRAF1	ENST00000540010.1	TSL:1	c.1020C>T	p.Pro340Pro	synonymous	Exon 8 of 9	ENSP00000443183.1	Q13077-1
	TRAF1	ENST00000871615.1		c.1020C>T	p.Pro340Pro	synonymous	Exon 7 of 8	ENSP00000541674.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104285 AN: 151860 Hom.: 36083 Cov.: 31

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.707

GnomAD2 exomes AF: 0.688 AC: 172859 AN: 251212 AF XY: 0.694

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.719

Gnomad ASJ exome AF: 0.734

Gnomad EAS exome AF: 0.705

Gnomad FIN exome AF: 0.564

Gnomad NFE exome AF: 0.651

Gnomad OTH exome AF: 0.682

GnomAD4 exome AF: 0.666 AC: 973581 AN: 1461578 Hom.: 326630 Cov.: 61 AF XY: 0.671 AC XY: 488185 AN XY: 727074

African (AFR) AF: 0.754 AC: 25250 AN: 33478

American (AMR) AF: 0.722 AC: 32290 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 19082 AN: 26136

East Asian (EAS) AF: 0.717 AC: 28471 AN: 39690

South Asian (SAS) AF: 0.821 AC: 70815 AN: 86224

European-Finnish (FIN) AF: 0.568 AC: 30347 AN: 53408

Middle Eastern (MID) AF: 0.756 AC: 4266 AN: 5646

European-Non Finnish (NFE) AF: 0.649 AC: 721609 AN: 1111914

Other (OTH) AF: 0.687 AC: 41451 AN: 60368

GnomAD4 genome AF: 0.687 AC: 104381 AN: 151978 Hom.: 36129 Cov.: 31 AF XY: 0.687 AC XY: 51043 AN XY: 74282

African (AFR) AF: 0.756 AC: 31346 AN: 41476

American (AMR) AF: 0.704 AC: 10733 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2582 AN: 3468

East Asian (EAS) AF: 0.720 AC: 3712 AN: 5158

South Asian (SAS) AF: 0.818 AC: 3943 AN: 4820

European-Finnish (FIN) AF: 0.577 AC: 6090 AN: 10552

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43810 AN: 67942

Other (OTH) AF: 0.706 AC: 1485 AN: 2104

Alfa AF: 0.674 Hom.: 52793

Bravo AF: 0.697

Asia WGS AF: 0.773 AC: 2685 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.0
DANN	Benign	0.65
PhyloP100		-1.0
Mutation Taster		=92/8	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: rs2239657; hg19: chr9-123671520; COSMIC: COSV65869103;