chr6-111580635-G-A

Variant names:

• chr6-111580635-G-A
• rs13196377
• NM_147686.4:c.830-246C>T

Variant summary

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

The NM_147686.4(TRAF3IP2):​c.830-246C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 152,084 control chromosomes in the GnomAD database, including 328 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 0.063 (328 hom., cov: 33)
• Consequence: TRAF3IP2 NM_147686.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 19 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP2	NM_147686.4	c.830-246C>T		intron_variant	Intron 2 of 8	ENST00000368761.11	NP_679211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF3IP2	ENST00000368761.11	c.830-246C>T		intron_variant	Intron 2 of 8	1	NM_147686.4	ENSP00000357750.5

Frequencies

GnomAD3 genomes AF: 0.0628 AC: 9537 AN: 151966 Hom.: 328 Cov.: 33

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0540

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0580

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0619

Gnomad OTH AF: 0.0650

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

GnomAD4 genome AF: 0.0628 AC: 9553 AN: 152084 Hom.: 328 Cov.: 33 AF XY: 0.0615 AC XY: 4575 AN XY: 74332

African (AFR) AF: 0.0755 AC: 3132 AN: 41472

American (AMR) AF: 0.0539 AC: 825 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3470

East Asian (EAS) AF: 0.000583 AC: 3 AN: 5150

South Asian (SAS) AF: 0.0398 AC: 192 AN: 4830

European-Finnish (FIN) AF: 0.0580 AC: 612 AN: 10556

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0619 AC: 4212 AN: 67996

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0576 Hom.: 244

Bravo AF: 0.0638

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.4
DANN	Benign	0.63
PhyloP100		1.1
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: rs13196377; hg19: chr6-111901838;