6-137871133-G-C

Position:

• chr6-137871133-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001270508.2(TNFAIP3):​c.-15-80G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,354,754 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0080 (11 hom., cov: 32)
  • Exomes 𝑓: 0.013 (126 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00801 (1219/152136) while in subpopulation NFE AF= 0.0138 (940/67994). AF 95% confidence interval is 0.0131. There are 11 homozygotes in gnomad4. There are 541 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1219 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.-15-80G>C		intron_variant		ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.-15-80G>C		intron_variant		5	NM_001270508.2	ENSP00000481570	P1

Frequencies

GnomAD3 genomes AF: 0.00801 AC: 1217 AN: 152018 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00297

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00692

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.00766

GnomAD4 exome AF: 0.0134 AC: 16060 AN: 1202618 Hom.: 126 AF XY: 0.0130 AC XY: 7782 AN XY: 596674

Gnomad4 AFR exome AF: 0.00247

Gnomad4 AMR exome AF: 0.00308

Gnomad4 ASJ exome AF: 0.00185

Gnomad4 EAS exome AF: 0.0000788

Gnomad4 SAS exome AF: 0.00190

Gnomad4 FIN exome AF: 0.00645

Gnomad4 NFE exome AF: 0.0160

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.00801 AC: 1219 AN: 152136 Hom.: 11 Cov.: 32 AF XY: 0.00728 AC XY: 541 AN XY: 74354

Gnomad4 AFR AF: 0.00296

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00692

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00380 Hom.: 0

Bravo AF: 0.00787

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.74

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: rs79608867; hg19: chr6-138192270;