chr9-120909335-C-T

Position:

• chr9-120909335-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_005658.5(TRAF1):​c.927G>A​(p.Leu309=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,614,162 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (59 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (56 hom.)
• Consequence: TRAF1 NM_005658.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.138

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=-0.47).
• BP6: Variant 9-120909335-C-T is Benign according to our data. Variant chr9-120909335-C-T is described in ClinVar as [Benign]. Clinvar id is 781187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.138 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2052/152316) while in subpopulation AFR AF= 0.0462 (1920/41558). AF 95% confidence interval is 0.0445. There are 59 homozygotes in gnomad4. There are 960 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF1	NM_005658.5	c.927G>A	p.Leu309=	synonymous_variant	7/8	ENST00000373887.8
TRAF1	NM_001190945.2	c.927G>A	p.Leu309=	synonymous_variant	8/9
TRAF1	NM_001190947.2	c.561G>A	p.Leu187=	synonymous_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF1	ENST00000373887.8	c.927G>A	p.Leu309=	synonymous_variant	7/8	1	NM_005658.5	P1
TRAF1	ENST00000540010.1	c.927G>A	p.Leu309=	synonymous_variant	8/9	1		P1
TRAF1	ENST00000546084.5	c.561G>A	p.Leu187=	synonymous_variant	5/6	2

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2044 AN: 152198 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.00379 AC: 954 AN: 251432 Hom.: 18 AF XY: 0.00285 AC XY: 387 AN XY: 135890

Gnomad AFR exome AF: 0.0476

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00170 AC: 2485 AN: 1461846 Hom.: 56 Cov.: 33 AF XY: 0.00152 AC XY: 1106 AN XY: 727216

Gnomad4 AFR exome AF: 0.0513

Gnomad4 AMR exome AF: 0.00364

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000274

Gnomad4 OTH exome AF: 0.00402

GnomAD4 genome AF: 0.0135 AC: 2052 AN: 152316 Hom.: 59 Cov.: 32 AF XY: 0.0129 AC XY: 960 AN XY: 74478

Gnomad4 AFR AF: 0.0462

Gnomad4 AMR AF: 0.00542

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00763 Hom.: 12

Bravo AF: 0.0161

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.3
DANN	Benign	0.67

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: rs112060909; hg19: chr9-123671613;