rs576438307

Variant names:

• chr6-111562947-GTTTC-G
• rs576438307
• NM_147686.4:c.1551+14_1551+17delGAAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_147686.4(TRAF3IP2):​c.1551+14_1551+17delGAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,585,614 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (2 hom.)
• Consequence: TRAF3IP2 NM_147686.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.490
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 6-111562947-GTTTC-G is Benign according to our data. Variant chr6-111562947-GTTTC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1115485.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00116 (176/152274) while in subpopulation AMR AF = 0.00288 (44/15296). AF 95% confidence interval is 0.0022. There are 0 homozygotes in GnomAd4. There are 97 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP2	NM_147686.4	MANE Select	c.1551+14_1551+17delGAAA		intron	N/A	NP_679211.2	O43734-2
	TRAF3IP2	NM_147200.3		c.1578+14_1578+17delGAAA		intron	N/A	NP_671733.2	O43734-1
	TRAF3IP2	NM_001164281.3		c.1548+14_1548+17delGAAA		intron	N/A	NP_001157753.1	O43734-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP2	ENST00000368761.11	TSL:1 MANE Select	c.1551+14_1551+17delGAAA		intron	N/A	ENSP00000357750.5	O43734-2
	TRAF3IP2	ENST00000340026.10	TSL:1	c.1578+14_1578+17delGAAA		intron	N/A	ENSP00000345984.6	O43734-1
	TRAF3IP2	ENST00000699910.1		c.1565_1568delGAAA	p.Arg522ThrfsTer5	frameshift	Exon 8 of 8	ENSP00000514682.1	A0A8V8TQD6

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 176 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000982 AC: 239 AN: 243272 AF XY: 0.000995

Gnomad AFR exome AF: 0.000314

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000463

Gnomad NFE exome AF: 0.00143

Gnomad OTH exome AF: 0.00151

GnomAD4 exome AF: 0.00164 AC: 2348 AN: 1433340 Hom.: 2 AF XY: 0.00153 AC XY: 1094 AN XY: 713804

African (AFR) AF: 0.000456 AC: 15 AN: 32886

American (AMR) AF: 0.00190 AC: 84 AN: 44252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25828

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84676

European-Finnish (FIN) AF: 0.000280 AC: 14 AN: 49950

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5694

European-Non Finnish (NFE) AF: 0.00199 AC: 2175 AN: 1091116

Other (OTH) AF: 0.000958 AC: 57 AN: 59468

GnomAD4 genome AF: 0.00116 AC: 176 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.00130 AC XY: 97 AN XY: 74450

African (AFR) AF: 0.000313 AC: 13 AN: 41556

American (AMR) AF: 0.00288 AC: 44 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000943 AC: 10 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00146 AC: 99 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00135 Hom.: 0

Bravo AF: 0.00148

ClinVar

ClinVar submissions as Germline

Significance: Likely 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
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism

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: rs576438307; hg19: chr6-111884150;