rs629953

Variant names:

• chr6-137873904-A-G
• rs629953
• NM_001270508.2:c.296-941A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-137873904-A-G
• chr6-137873904-A-T

Variant summary

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

The NM_001270508.2(TNFAIP3):​c.296-941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,148 control chromosomes in the GnomAD database, including 23,628 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 0.51 (23628 hom., cov: 32)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 12 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.296-941A>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.296-941A>G		intron_variant	Intron 2 of 8	5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78074 AN: 152030 Hom.: 23631 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.513 AC: 78074 AN: 152148 Hom.: 23628 Cov.: 32 AF XY: 0.518 AC XY: 38555 AN XY: 74374

African (AFR) AF: 0.174 AC: 7217 AN: 41526

American (AMR) AF: 0.562 AC: 8586 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1984 AN: 3470

East Asian (EAS) AF: 0.852 AC: 4418 AN: 5184

South Asian (SAS) AF: 0.667 AC: 3220 AN: 4826

European-Finnish (FIN) AF: 0.648 AC: 6845 AN: 10568

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43938 AN: 67970

Other (OTH) AF: 0.546 AC: 1154 AN: 2114

Alfa AF: 0.527 Hom.: 3307

Bravo AF: 0.494

Asia WGS AF: 0.675 AC: 2344 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		0.26
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: rs629953; hg19: chr6-138195041;