rs186097801

Variant names:

• chr6-111559489-G-A
• rs186097801
• NM_147686.4:c.1614C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-111559489-G-A
• chr6-111559489-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_147686.4(TRAF3IP2):​c.1614C>T​(p.Asn538Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,614,026 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000091 (0 hom.)
• Consequence: TRAF3IP2 NM_147686.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.805
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-111559489-G-A is Benign according to our data. Variant chr6-111559489-G-A is described in ClinVar as Benign. ClinVar VariationId is 474038.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.805 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000125 (19/152264) while in subpopulation AMR AF = 0.00111 (17/15304). AF 95% confidence interval is 0.000707. There are 1 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147686.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP2	NM_147686.4	MANE Select	c.1614C>T	p.Asn538Asn	synonymous	Exon 9 of 9	NP_679211.2
	TRAF3IP2	NM_147200.3		c.1641C>T	p.Asn547Asn	synonymous	Exon 10 of 10	NP_671733.2
	TRAF3IP2	NM_001164281.3		c.1611C>T	p.Asn537Asn	synonymous	Exon 9 of 9	NP_001157753.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP2	ENST00000368761.11	TSL:1 MANE Select	c.1614C>T	p.Asn538Asn	synonymous	Exon 9 of 9	ENSP00000357750.5
	TRAF3IP2	ENST00000340026.10	TSL:1	c.1641C>T	p.Asn547Asn	synonymous	Exon 10 of 10	ENSP00000345984.6
	TRAF3IP2	ENST00000651547.2		c.1614C>T	p.Asn538Asn	synonymous	Exon 11 of 11	ENSP00000514681.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152148 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000453 AC: 113 AN: 249302 AF XY: 0.000297

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00315

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.0000910 AC: 133 AN: 1461762 Hom.: 0 Cov.: 30 AF XY: 0.0000715 AC XY: 52 AN XY: 727168

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00266 AC: 119 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111946

Other (OTH) AF: 0.000182 AC: 11 AN: 60392

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152264 Hom.: 1 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74464

African (AFR) AF: 0.0000481 AC: 2 AN: 41540

American (AMR) AF: 0.00111 AC: 17 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000177 Hom.: 0

Bravo AF: 0.000389

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Candidiasis, familial, 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.1
DANN	Benign	0.81
PhyloP100		0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs186097801; hg19: chr6-111880692;