rs10484479

Positions:

• chr6-111555782-T-C

Variant summary

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

The NM_147686.4(TRAF3IP2):​c.*3623A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 152,228 control chromosomes in the GnomAD database, including 743 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 0.082 (743 hom., cov: 32)
• Consequence: TRAF3IP2 NM_147686.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

Genes affected

TRAF3IP2 (HGNC:1343): (TRAF3 interacting protein 2) This gene encodes a protein involved in regulating responses to cytokines by members of the Rel/NF-kappaB transcription factor family. These factors play a central role in innate immunity in response to pathogens, inflammatory signals and stress. This gene product interacts with TRAF proteins (tumor necrosis factor receptor-associated factors) and either I-kappaB kinase or MAP kinase to activate either NF-kappaB or Jun kinase. Several alternative transcripts encoding different isoforms have been identified. Another transcript, which does not encode a protein and is transcribed in the opposite orientation, has been identified. Overexpression of this transcript has been shown to reduce expression of at least one of the protein encoding transcripts, suggesting it has a regulatory role in the expression of this gene. [provided by RefSeq, Aug 2009]

TRAF3IP2-AS1 (HGNC:40005): (TRAF3IP2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3IP2	NM_147686.4	c.*3623A>G		3_prime_UTR_variant	9/9	ENST00000368761.11	NP_679211.2
TRAF3IP2-AS1	NR_034108.1	n.195-18839T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3IP2	ENST00000368761.11	c.*3623A>G		3_prime_UTR_variant	9/9	1	NM_147686.4	ENSP00000357750	P4
TRAF3IP2-AS1	ENST00000687951.2	n.155-18839T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12473 AN: 152110 Hom.: 743 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0785

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0819 AC: 12467 AN: 152228 Hom.: 743 Cov.: 32 AF XY: 0.0853 AC XY: 6346 AN XY: 74428

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.0613

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.0592

Gnomad4 SAS AF: 0.0877

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0786

Alfa AF: 0.0987 Hom.: 1134

Bravo AF: 0.0698

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10484479; hg19: chr6-111876985;