rs3750512

Variant names:

• chr9-136926616-G-A
• rs3750512
• ENST00000850853.1:c.*715G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000850853.1(TRAF2):​c.*715G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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: TRAF2 ENST00000850853.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 16 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000850853.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF2	NM_021138.4	MANE Select	c.*715G>A		downstream_gene	N/A	NP_066961.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF2	ENST00000850853.1		c.*715G>A		3_prime_UTR	Exon 11 of 11	ENSP00000520942.1
	TRAF2	ENST00000882552.1		c.*715G>A		3_prime_UTR	Exon 12 of 12	ENSP00000552611.1
	TRAF2	ENST00000882555.1		c.*715G>A		3_prime_UTR	Exon 11 of 11	ENSP00000552614.1

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

African (AFR) AF: 0.846 AC: 22 AN: 26

American (AMR) AF: 0.489 AC: 639 AN: 1308

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 7 AN: 12

East Asian (EAS) AF: 0.730 AC: 143 AN: 196

South Asian (SAS) AF: 0.743 AC: 226 AN: 304

European-Finnish (FIN) AF: 0.571 AC: 8 AN: 14

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.611 AC: 1463 AN: 2394

Other (OTH) AF: 0.632 AC: 120 AN: 190

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

African (AFR) AF: 0.623 AC: 25886 AN: 41528

American (AMR) AF: 0.538 AC: 8219 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2330 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4392 AN: 5174

South Asian (SAS) AF: 0.749 AC: 3617 AN: 4832

European-Finnish (FIN) AF: 0.658 AC: 6975 AN: 10602

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42313 AN: 67976

Other (OTH) AF: 0.641 AC: 1356 AN: 2114

Alfa AF: 0.622 Hom.: 93068

Bravo AF: 0.616

Asia WGS AF: 0.766 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.7
DANN	Benign	0.62
PhyloP100		-0.058

Splicing

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

Other links and lift over

dbSNP: rs3750512; hg19: chr9-139821068;