rs661561

chr6-137876194-A-Cchr6-137876194-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001270508.2(TNFAIP3):c.805+28A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 1,583,506 control chromosomes in the GnomAD database, including 319,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (23620 hom., cov: 32)
  • Exomes 𝑓: 0.64 (295461 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.50

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-137876194-A-C is Benign according to our data. Variant chr6-137876194-A-C is described in ClinVar as [Benign]. Clinvar id is 1281403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFAIP3	NM_001270508.2	c.805+28A>C		intron_variant		ENST00000612899.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.805+28A>C		intron_variant		5	NM_001270508.2	P1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78072 AN: 152004 Hom.: 23623 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.550

GnomAD3 exomes AF: 0.620 AC: 148964 AN: 240196 Hom.: 48370 AF XY: 0.631 AC XY: 81907 AN XY: 129860

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.577

Gnomad ASJ exome AF: 0.592

Gnomad EAS exome AF: 0.856

Gnomad SAS exome AF: 0.661

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.647

Gnomad OTH exome AF: 0.631

GnomAD4 exome AF: 0.637 AC: 911558 AN: 1431386 Hom.: 295461 Cov.: 25 AF XY: 0.639 AC XY: 455444 AN XY: 712590

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.574

Gnomad4 ASJ exome AF: 0.584

Gnomad4 EAS exome AF: 0.859

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.646

Gnomad4 OTH exome AF: 0.615

GnomAD4 genome AF: 0.513 AC: 78071 AN: 152120 Hom.: 23620 Cov.: 32 AF XY: 0.518 AC XY: 38547 AN XY: 74360

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.547

Alfa AF: 0.625 Hom.: 29474

Bravo AF: 0.494

Asia WGS AF: 0.673 AC: 2339 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.30
Dann	Benign	0.42

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: rs661561; hg19: chr6-138197331; COSMIC: COSV52801907; COSMIC: COSV52801907;