rs2811757

Positions:

• chr9-136901052-A-G
• chr9-136901052-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000247668.7(TRAF2):​c.366+532A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,214 control chromosomes in the GnomAD database, including 48,491 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 0.80 (48491 hom., cov: 33)
• Consequence: TRAF2 ENST00000247668.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234

Genes affected

TRAF2 (HGNC:12032): (TNF receptor associated factor 2) The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF1 interacts with the inhibitor-of-apoptosis proteins (IAPs), and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. BIRC2/c-IAP1, an apoptosis inhibitor possessing ubiquitin ligase activity, can unbiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF2	NM_021138.4	c.366+532A>G		intron_variant		ENST00000247668.7	NP_066961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF2	ENST00000247668.7	c.366+532A>G		intron_variant		1	NM_021138.4	ENSP00000247668	P1
TRAF2	ENST00000419057.5	c.366+532A>G		intron_variant		3		ENSP00000405860
TRAF2	ENST00000429509.5	c.366+532A>G		intron_variant		3		ENSP00000406524
TRAF2	ENST00000474950.5	n.41+532A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.796 AC: 121126 AN: 152094 Hom.: 48468 Cov.: 33

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.774

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.796 AC: 121206 AN: 152214 Hom.: 48491 Cov.: 33 AF XY: 0.796 AC XY: 59262 AN XY: 74420

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.777

Alfa AF: 0.782 Hom.: 20948

Bravo AF: 0.786

Asia WGS AF: 0.821 AC: 2854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.68

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: rs2811757; hg19: chr9-139795504;