6-137871187-CTT-CTTT

Position:

• chr6-137871187-CTT-CTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001270508.2(TNFAIP3):​c.-15-15dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,077,466 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 32)
  • Exomes 𝑓: 0.014 (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.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00112 (165/146674) while in subpopulation SAS AF= 0.0123 (57/4622). AF 95% confidence interval is 0.00977. There are 2 homozygotes in gnomad4. There are 94 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 165 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 165 AN: 146600 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000576

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000272

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00314

Gnomad SAS AF: 0.0125

Gnomad FIN AF: 0.000318

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000922

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0135 AC: 12568 AN: 930792 Hom.: 0 Cov.: 18 AF XY: 0.0134 AC XY: 6228 AN XY: 463078

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.00878

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.0116

Gnomad4 SAS exome AF: 0.0261

Gnomad4 FIN exome AF: 0.00958

Gnomad4 NFE exome AF: 0.0132

Gnomad4 OTH exome AF: 0.0132

GnomAD4 genome AF: 0.00112 AC: 165 AN: 146674 Hom.: 2 Cov.: 32 AF XY: 0.00132 AC XY: 94 AN XY: 71410

Gnomad4 AFR AF: 0.000599

Gnomad4 AMR AF: 0.000272

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00315

Gnomad4 SAS AF: 0.0123

Gnomad4 FIN AF: 0.000318

Gnomad4 NFE AF: 0.000922

Gnomad4 OTH AF: 0.00

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;