NM_001270508.2:c.296-289T>C

Variant names:

• chr6-137874556-T-C
• rs643177
• NM_001270508.2:c.296-289T>C

Variant summary

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

The NM_001270508.2(TNFAIP3):​c.296-289T>C 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 152,128 control chromosomes in the GnomAD database, including 38,488 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 (38488 hom., cov: 32)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 27 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: Labcorp Genetics (formerly Invitae)
• hereditary pediatric Behçet-like disease

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

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.296-289T>C		intron_variant	Intron 2 of 8	ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.296-289T>C		intron_variant	Intron 2 of 8	5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107778 AN: 152010 Hom.: 38456 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.727

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: 107860 AN: 152128 Hom.: 38488 Cov.: 32 AF XY: 0.708 AC XY: 52653 AN XY: 74376

African (AFR) AF: 0.652 AC: 27064 AN: 41484

American (AMR) AF: 0.726 AC: 11105 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2405 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4709 AN: 5182

South Asian (SAS) AF: 0.763 AC: 3684 AN: 4826

European-Finnish (FIN) AF: 0.673 AC: 7117 AN: 10582

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49399 AN: 67968

Other (OTH) AF: 0.730 AC: 1544 AN: 2116

Alfa AF: 0.725 Hom.: 168150

Bravo AF: 0.710

Asia WGS AF: 0.811 AC: 2819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.59
PhyloP100		-1.0
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: rs643177; hg19: chr6-138195693; COSMIC: COSV52801899; COSMIC: COSV52801899;