rs3750512

Positions:

• chr9-136926616-G-A
• chr9-136926616-G-C
• chr9-136926616-G-T

Variant summary

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

The variant allele was found at a frequency of 0.629 in 156,638 control chromosomes in the GnomAD database, including 31,299 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 0.63 (30462 hom., cov: 34)
  • Exomes 𝑓: 0.59 (837 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

Genes affected

(HGNC:):

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF2	NM_021138.4	c.*715G>A		downstream_gene_variant		ENST00000247668.7	NP_066961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF2	ENST00000247668.7	c.*715G>A		downstream_gene_variant		1	NM_021138.4	ENSP00000247668.2

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95790 AN: 152074 Hom.: 30448 Cov.: 34

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.591 AC: 2628 AN: 4446 Hom.: 837 Cov.: 0 AF XY: 0.597 AC XY: 1362 AN XY: 2282

Gnomad4 AFR exome AF: 0.846

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.730

Gnomad4 SAS exome AF: 0.743

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.611

Gnomad4 OTH exome AF: 0.632

GnomAD4 genome AF: 0.630 AC: 95857 AN: 152192 Hom.: 30462 Cov.: 34 AF XY: 0.634 AC XY: 47181 AN XY: 74406

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.641

Alfa AF: 0.625 Hom.: 59231

Bravo AF: 0.616

Asia WGS AF: 0.766 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.7
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3750512; hg19: chr9-139821068;