rs6684874

Variant names:

• chr1-211358718-A-G
• rs6684874
• NM_001033910.3:c.379-1194A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-211358718-A-G
• chr1-211358718-A-T

Variant summary

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

The NM_001033910.3(TRAF5):​c.379-1194A>G 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: 28)
• Consequence: TRAF5 NM_001033910.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 5 publications found

Genes affected

TRAF5 (HGNC:12035): (TNF receptor associated factor 5) The scaffold protein encoded by this gene is a member of the tumor necrosis factor receptor-associated factor (TRAF) protein family and contains a meprin and TRAF homology (MATH) domain, a RING-type zinc finger, and two TRAF-type zinc fingers. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein is one of the components of a multiple protein complex which binds to tumor necrosis factor (TNF) receptor cytoplasmic domains and mediates TNF-induced activation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

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=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033910.3. 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
	TRAF5	NM_001033910.3	MANE Select	c.379-1194A>G		intron	N/A	NP_001029082.1	O00463-1
	TRAF5	NM_001319207.2		c.379-1161A>G		intron	N/A	NP_001306136.1	O00463-2
	TRAF5	NM_004619.4		c.379-1194A>G		intron	N/A	NP_004610.1	O00463-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF5	ENST00000261464.10	TSL:1 MANE Select	c.379-1194A>G		intron	N/A	ENSP00000261464.5	O00463-1
	TRAF5	ENST00000367004.3	TSL:1	c.379-1194A>G		intron	N/A	ENSP00000355971.3	O00463-1
	TRAF5	ENST00000939501.1		c.379-1161A>G		intron	N/A	ENSP00000609560.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.48
DANN	Benign	0.21
PhyloP100		-0.23

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6684874;

hg19: chr1-211532060;