rs10781522

Variant names:

• chr9-136920601-G-A
• rs10781522
• NM_021138.4:c.960+86G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-136920601-G-A
• chr9-136920601-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000247668.7(TRAF2):​c.960+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,463,100 control chromosomes in the GnomAD database, including 274,169 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 0.59 (27077 hom., cov: 32)
  • Exomes 𝑓: 0.61 (247092 hom.)
• Consequence: TRAF2 ENST00000247668.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000247668.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF2	NM_021138.4	MANE Select	c.960+86G>A		intron	N/A	NP_066961.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF2	ENST00000247668.7	TSL:1 MANE Select	c.960+86G>A		intron	N/A	ENSP00000247668.2
	TRAF2	ENST00000850853.1		c.960+86G>A		intron	N/A	ENSP00000520942.1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90259 AN: 151896 Hom.: 27076 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.591

GnomAD4 exome AF: 0.612 AC: 801787 AN: 1311088 Hom.: 247092 AF XY: 0.615 AC XY: 393262 AN XY: 639474

African (AFR) AF: 0.535 AC: 15659 AN: 29290

American (AMR) AF: 0.460 AC: 11938 AN: 25936

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 13188 AN: 19820

East Asian (EAS) AF: 0.745 AC: 26673 AN: 35816

South Asian (SAS) AF: 0.726 AC: 48369 AN: 66636

European-Finnish (FIN) AF: 0.624 AC: 24252 AN: 38878

Middle Eastern (MID) AF: 0.651 AC: 3287 AN: 5050

European-Non Finnish (NFE) AF: 0.604 AC: 624779 AN: 1035174

Other (OTH) AF: 0.617 AC: 33642 AN: 54488

GnomAD4 genome AF: 0.594 AC: 90288 AN: 152012 Hom.: 27077 Cov.: 32 AF XY: 0.596 AC XY: 44298 AN XY: 74306

African (AFR) AF: 0.537 AC: 22265 AN: 41452

American (AMR) AF: 0.513 AC: 7834 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2300 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3699 AN: 5160

South Asian (SAS) AF: 0.746 AC: 3592 AN: 4816

European-Finnish (FIN) AF: 0.623 AC: 6587 AN: 10578

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 41990 AN: 67952

Other (OTH) AF: 0.596 AC: 1257 AN: 2108

Alfa AF: 0.605 Hom.: 101077

Bravo AF: 0.577

Asia WGS AF: 0.676 AC: 2352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.57
DANN	Benign	0.70
PhyloP100		-1.5
Mutation Taster		=100/0	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: rs10781522; hg19: chr9-139815053;