6-137871187-CTT-CT

Position:

• chr6-137871187-CTT-CT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001270508.2(TNFAIP3):​c.-15-15delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 869,264 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.-15-15delT		intron_variant		ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.-15-15delT		intron_variant		5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes AF: 0.000635 AC: 93 AN: 146394 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000501

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00198

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.000785

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00182

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.000318

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0706 AC: 51041 AN: 722800 Hom.: 0 Cov.: 18 AF XY: 0.0751 AC XY: 26704 AN XY: 355816

Gnomad4 AFR exome AF: 0.0776

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.0609

Gnomad4 OTH exome AF: 0.0792

GnomAD4 genome AF: 0.000642 AC: 94 AN: 146464 Hom.: 0 Cov.: 32 AF XY: 0.000800 AC XY: 57 AN XY: 71286

Gnomad4 AFR AF: 0.000499

Gnomad4 AMR AF: 0.00198

Gnomad4 ASJ AF: 0.000294

Gnomad4 EAS AF: 0.000787

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00182

Gnomad4 NFE AF: 0.000318

Gnomad4 OTH AF: 0.000497

ClinVar

Not reported in ClinVar

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: rs3214646; hg19: chr6-138192324;