rs5029939

Variant names:

• chr6-137874586-C-G
• rs5029939
• NM_001270508.2:c.296-259C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270508.2(TNFAIP3):​c.296-259C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,196 control chromosomes in the GnomAD database, including 2,826 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 0.13 (2826 hom., cov: 33)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.296-259C>G		intron_variant	Intron 2 of 8	ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.296-259C>G		intron_variant	Intron 2 of 8	5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19152 AN: 152078 Hom.: 2816 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0313

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.126 AC: 19200 AN: 152196 Hom.: 2826 Cov.: 33 AF XY: 0.122 AC XY: 9092 AN XY: 74424

Gnomad4 AFR AF: 0.362 AC: 0.361698 AN: 0.361698

Gnomad4 AMR AF: 0.0732 AC: 0.0731835 AN: 0.0731835

Gnomad4 ASJ AF: 0.0441 AC: 0.0440668 AN: 0.0440668

Gnomad4 EAS AF: 0.0430 AC: 0.0429838 AN: 0.0429838

Gnomad4 SAS AF: 0.0317 AC: 0.0317033 AN: 0.0317033

Gnomad4 FIN AF: 0.0167 AC: 0.0166698 AN: 0.0166698

Gnomad4 NFE AF: 0.0313 AC: 0.0312886 AN: 0.0312886

Gnomad4 OTH AF: 0.110 AC: 0.110322 AN: 0.110322

Alfa AF: 0.0797 Hom.: 211

Bravo AF: 0.140

Asia WGS AF: 0.0510 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs5029939; hg19: chr6-138195723;