9-120909242-G-A

Position:

• chr9-120909242-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005658.5(TRAF1):​c.1020C>T​(p.Pro340=) 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, single submitter B:1
• Conservation: PhyloP100: -1.01

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF1	NM_005658.5	c.1020C>T	p.Pro340=	synonymous_variant	7/8	ENST00000373887.8
TRAF1	NM_001190945.2	c.1020C>T	p.Pro340=	synonymous_variant	8/9
TRAF1	NM_001190947.2	c.654C>T	p.Pro218=	synonymous_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF1	ENST00000373887.8	c.1020C>T	p.Pro340=	synonymous_variant	7/8	1	NM_005658.5	P1
TRAF1	ENST00000540010.1	c.1020C>T	p.Pro340=	synonymous_variant	8/9	1		P1
TRAF1	ENST00000546084.5	c.654C>T	p.Pro218=	synonymous_variant	5/6	2

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

GnomAD3 exomes AF: 0.688 AC: 172859 AN: 251212 Hom.: 60049 AF XY: 0.694 AC XY: 94282 AN XY: 135772

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 SAS exome AF: 0.816

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

Gnomad4 AFR exome AF: 0.754

Gnomad4 AMR exome AF: 0.722

Gnomad4 ASJ exome AF: 0.730

Gnomad4 EAS exome AF: 0.717

Gnomad4 SAS exome AF: 0.821

Gnomad4 FIN exome AF: 0.568

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.687

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

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.706

Alfa AF: 0.674 Hom.: 45489

Bravo AF: 0.697

Asia WGS AF: 0.773 AC: 2685 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.0
DANN	Benign	0.65

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: rs2239657; hg19: chr9-123671520; COSMIC: COSV65869103;