6-137876687-C-T

Variant names:

• chr6-137876687-C-T
• rs582757
• NM_001270508.2:c.806-389C>T

Variant summary

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

The NM_001270508.2(TNFAIP3):​c.806-389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,172 control chromosomes in the GnomAD database, including 38,469 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 0.71 (38469 hom., cov: 33)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• Publications: 59 publications found

Genes affected

TNFAIP3 (HGNC:11896): (TNF alpha induced protein 3) This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded by this gene is a zinc finger protein and ubiqitin-editing enzyme, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. The encoded protein, which has both ubiquitin ligase and deubiquitinase activities, is involved in the cytokine-mediated immune and inflammatory responses. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2012]

TNFAIP3 Gene-Disease associations (from GenCC):

• autoinflammatory syndrome, familial, Behcet-like 1

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hereditary pediatric Behçet-like disease

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287393 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270508.2. 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
	TNFAIP3	NM_001270508.2	MANE Select	c.806-389C>T		intron	N/A	NP_001257437.1	P21580
	TNFAIP3	NM_001270507.2		c.806-389C>T		intron	N/A	NP_001257436.1	P21580
	TNFAIP3	NM_006290.4		c.806-389C>T		intron	N/A	NP_006281.1	P21580

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP3	ENST00000612899.5	TSL:5 MANE Select	c.806-389C>T		intron	N/A	ENSP00000481570.1	P21580
	TNFAIP3	ENST00000237289.8	TSL:1	c.806-389C>T		intron	N/A	ENSP00000237289.4	P21580
	TNFAIP3	ENST00000420009.6	TSL:3	c.806-389C>T		intron	N/A	ENSP00000401562.2	P21580

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107781 AN: 152054 Hom.: 38437 Cov.: 33

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.709 AC: 107864 AN: 152172 Hom.: 38469 Cov.: 33 AF XY: 0.708 AC XY: 52659 AN XY: 74396

African (AFR) AF: 0.653 AC: 27113 AN: 41496

American (AMR) AF: 0.726 AC: 11101 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2396 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4710 AN: 5182

South Asian (SAS) AF: 0.759 AC: 3664 AN: 4826

European-Finnish (FIN) AF: 0.673 AC: 7116 AN: 10580

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49391 AN: 68000

Other (OTH) AF: 0.730 AC: 1541 AN: 2110

Alfa AF: 0.722 Hom.: 56072

Bravo AF: 0.710

Asia WGS AF: 0.807 AC: 2804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.2
DANN	Benign	0.60
PhyloP100		0.56
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: rs582757; hg19: chr6-138197824; COSMIC: COSV52797707; COSMIC: COSV52797707;