rs2307859

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.296-15_296-13delCCT		intron_variant		ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.296-15_296-13delCCT		intron_variant		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

GnomAD3 exomes AF: 0.615 AC: 151478 AN: 246108 Hom.: 48869 AF XY: 0.626 AC XY: 83189 AN XY: 132970

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 SAS exome AF: 0.658

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

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.567

Gnomad4 ASJ exome AF: 0.581

Gnomad4 EAS exome AF: 0.857

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.645

Gnomad4 OTH exome AF: 0.614

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

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.546

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 30, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

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

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs2307859; hg19: chr6-138195961;