rs2303439

Variant names:

• chr11-36492740-T-A
• rs2303439
• NM_004620.4:c.679-112A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-36492740-T-A
• chr11-36492740-T-C
• chr11-36492740-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004620.4(TRAF6):​c.679-112A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000033 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRAF6 NM_004620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 12 publications found

Genes affected

TRAF6 (HGNC:12036): (TNF receptor associated factor 6) The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from, members of the TNF receptor superfamily. This protein has an amino terminal RING domain which is followed by four zinc-finger motifs, a central coiled-coil region and a highly conserved carboxyl terminal domain, known as the TRAF-C domain and mediates signaling from members of the TNF receptor superfamily as well as the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/RANCE and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. This protein also interacts with the transforming growth factor (TGF) beta receptor complex and is required for Smad-independent activation of the JNK and p38 kinases. The protein encoded by this gene is a key molecule in antiviral innate and antigen-specific immune responses. [provided by RefSeq, Nov 2021]

TRAF6 Gene-Disease associations (from GenCC):

• autosomal dominant hypohidrotic ectodermal dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF6	NM_004620.4	c.679-112A>T		intron_variant	Intron 5 of 6	ENST00000526995.6	NP_004611.1
TRAF6	NM_145803.3	c.679-112A>T		intron_variant	Intron 6 of 7		NP_665802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF6	ENST00000526995.6	c.679-112A>T		intron_variant	Intron 5 of 6	1	NM_004620.4	ENSP00000433623.1
TRAF6	ENST00000348124.5	c.679-112A>T		intron_variant	Intron 6 of 7	1		ENSP00000337853.5
TRAF6	ENST00000529150.1	n.224-112A>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000326 AC: 2 AN: 614440 Hom.: 0 AF XY: 0.00000610 AC XY: 2 AN XY: 327868

African (AFR) AF: 0.00 AC: 0 AN: 15438

American (AMR) AF: 0.00 AC: 0 AN: 25656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16732

East Asian (EAS) AF: 0.00 AC: 0 AN: 34868

South Asian (SAS) AF: 0.00 AC: 0 AN: 55536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2754

European-Non Finnish (NFE) AF: 0.00000520 AC: 2 AN: 384364

Other (OTH) AF: 0.00 AC: 0 AN: 31318

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.57
PhyloP100		-1.2

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: rs2303439; hg19: chr11-36514290;