rs5029930

Variant names:

• chr6-137869547-A-C
• rs5029930
• NM_001270508.2:c.-15-1666A>C

Variant summary

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

The NM_001270508.2(TNFAIP3):​c.-15-1666A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,146 control chromosomes in the GnomAD database, including 5,038 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 (5038 hom., cov: 32)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• autoinflammatory syndrome, familial, Behcet-like 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary pediatric Behçet-like disease

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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 rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.-15-1666A>C		intron_variant	Intron 1 of 8	ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.-15-1666A>C		intron_variant	Intron 1 of 8	5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29130 AN: 152028 Hom.: 5017 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.0978

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.192 AC: 29202 AN: 152146 Hom.: 5038 Cov.: 32 AF XY: 0.186 AC XY: 13818 AN XY: 74380

African (AFR) AF: 0.465 AC: 19273 AN: 41416

American (AMR) AF: 0.165 AC: 2518 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3472

East Asian (EAS) AF: 0.0565 AC: 293 AN: 5186

South Asian (SAS) AF: 0.0971 AC: 469 AN: 4830

European-Finnish (FIN) AF: 0.0252 AC: 268 AN: 10624

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0802 AC: 5456 AN: 68000

Other (OTH) AF: 0.179 AC: 379 AN: 2114

Alfa AF: 0.182 Hom.: 1294

Bravo AF: 0.212

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.54
PhyloP100		-0.18
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

Other links and lift over

dbSNP: rs5029930; hg19: chr6-138190684;