rs5029926

Positions:

• chr6-137868378-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270508.2(TNFAIP3):​c.-16+836A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,198 control chromosomes in the GnomAD database, including 5,022 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 0.19 (5022 hom., cov: 32)
  • Exomes 𝑓: 0.074 (0 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFAIP3	NM_001270508.2	c.-16+836A>G		intron_variant		ENST00000612899.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.-16+836A>G		intron_variant		5	NM_001270508.2	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29067 AN: 151932 Hom.: 5003 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.0743 AC: 11 AN: 148 Hom.: 0 AF XY: 0.0476 AC XY: 4 AN XY: 84

Gnomad4 EAS exome AF: 0.0809

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.192 AC: 29130 AN: 152050 Hom.: 5022 Cov.: 32 AF XY: 0.186 AC XY: 13822 AN XY: 74350

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0555

Gnomad4 SAS AF: 0.0971

Gnomad4 FIN AF: 0.0253

Gnomad4 NFE AF: 0.0803

Gnomad4 OTH AF: 0.173

Alfa AF: 0.142 Hom.: 627

Bravo AF: 0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.73
DANN	Benign	0.55

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: rs5029926; hg19: chr6-138189515; COSMIC: COSV52797655; COSMIC: COSV52797655;