rs598493

Variant names:

• chr6-137874265-T-C
• rs598493
• NM_001270508.2:c.296-580T>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.296-580T>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 152,064 control chromosomes in the GnomAD database, including 38,496 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 (38496 hom., cov: 32)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 12 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=-0.83).
• 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.296-580T>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.296-580T>C		intron_variant	Intron 2 of 8	5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107778 AN: 151946 Hom.: 38464 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.727

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: 152064 Hom.: 38496 Cov.: 32 AF XY: 0.708 AC XY: 52656 AN XY: 74336

African (AFR) AF: 0.653 AC: 27049 AN: 41430

American (AMR) AF: 0.728 AC: 11130 AN: 15298

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

East Asian (EAS) AF: 0.909 AC: 4707 AN: 5180

South Asian (SAS) AF: 0.764 AC: 3689 AN: 4830

European-Finnish (FIN) AF: 0.673 AC: 7103 AN: 10560

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

European-Non Finnish (NFE) AF: 0.727 AC: 49405 AN: 67978

Other (OTH) AF: 0.730 AC: 1541 AN: 2112

Alfa AF: 0.708 Hom.: 8949

Bravo AF: 0.711

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	-0.83
CADD	Benign	2.4
DANN	Benign	0.33
PhyloP100		-0.46
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: rs598493; hg19: chr6-138195402;