rs2307859

Variant names:

• chr6-137874824-TCTC-T
• rs2307859
• NM_001270508.2:c.296-15_296-13delCCT

Your query was ambiguous. Multiple possible variants found:

• chr6-137874824-TCTC-T
• chr6-137874824-TCTC-TCTCCTC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001270508.2(TNFAIP3):​c.296-15_296-13delCCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,603,882 control chromosomes in the GnomAD database, including 322,124 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (23464 hom., cov: 0)
  • Exomes 𝑓: 0.64 (298660 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.282
• Publications: 9 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 -16 ACMG points.

• BP6: Variant 6-137874824-TCTC-T is Benign according to our data. Variant chr6-137874824-TCTC-T is described in ClinVar as Benign. ClinVar VariationId is 993326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.296-15_296-13delCCT		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.296-20_296-18delCTC		intron_variant	Intron 2 of 8	5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77779 AN: 151574 Hom.: 23466 Cov.: 0

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.548

GnomAD2 exomes AF: 0.615 AC: 151478 AN: 246108 AF XY: 0.626

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.585

Gnomad EAS exome AF: 0.854

Gnomad FIN exome AF: 0.637

Gnomad NFE exome AF: 0.642

Gnomad OTH exome AF: 0.627

GnomAD4 exome AF: 0.635 AC: 922830 AN: 1452188 Hom.: 298660 AF XY: 0.638 AC XY: 459894 AN XY: 721190

African (AFR) AF: 0.165 AC: 5437 AN: 33008

American (AMR) AF: 0.567 AC: 24691 AN: 43582

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 15040 AN: 25892

East Asian (EAS) AF: 0.857 AC: 33853 AN: 39484

South Asian (SAS) AF: 0.661 AC: 56538 AN: 85594

European-Finnish (FIN) AF: 0.640 AC: 34081 AN: 53276

Middle Eastern (MID) AF: 0.599 AC: 3345 AN: 5588

European-Non Finnish (NFE) AF: 0.645 AC: 713028 AN: 1105850

Other (OTH) AF: 0.614 AC: 36817 AN: 59914

GnomAD4 genome AF: 0.513 AC: 77781 AN: 151694 Hom.: 23464 Cov.: 0 AF XY: 0.517 AC XY: 38342 AN XY: 74092

African (AFR) AF: 0.176 AC: 7290 AN: 41432

American (AMR) AF: 0.560 AC: 8537 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1972 AN: 3462

East Asian (EAS) AF: 0.850 AC: 4374 AN: 5144

South Asian (SAS) AF: 0.666 AC: 3199 AN: 4804

European-Finnish (FIN) AF: 0.645 AC: 6748 AN: 10470

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43802 AN: 67826

Other (OTH) AF: 0.546 AC: 1151 AN: 2108

Alfa AF: 0.581 Hom.: 5013

Bravo AF: 0.494

Asia WGS AF: 0.675 AC: 2345 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 30, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 79% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

Autoinflammatory syndrome, familial, Behcet-like Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autoinflammatory syndrome, familial, Behcet-like 1 Benign:1

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28
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: rs2307859; hg19: chr6-138195961;