6-137871187-CTT-CT

Variant names:

• chr6-137871187-CT-C
• rs3214646
• NM_001270508.2:c.-15-15delT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001270508.2(TNFAIP3):​c.-15-15delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 869,264 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.-15-15delT		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.-15-25delT		intron_variant	Intron 1 of 8	5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes AF: 0.000635 AC: 93 AN: 146394 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000501

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00198

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.000785

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00182

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.000318

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.253 AC: 15662 AN: 61868 AF XY: 0.256

Gnomad AFR exome AF: 0.240

Gnomad AMR exome AF: 0.271

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.253

Gnomad FIN exome AF: 0.219

Gnomad NFE exome AF: 0.248

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.0706 AC: 51041 AN: 722800 Hom.: 0 Cov.: 18 AF XY: 0.0751 AC XY: 26704 AN XY: 355816

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0776 AC: 1181 AN: 15222

American (AMR) AF: 0.140 AC: 2367 AN: 16894

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 1221 AN: 10864

East Asian (EAS) AF: 0.111 AC: 1764 AN: 15870

South Asian (SAS) AF: 0.120 AC: 4498 AN: 37484

European-Finnish (FIN) AF: 0.116 AC: 2925 AN: 25178

Middle Eastern (MID) AF: 0.0453 AC: 152 AN: 3352

European-Non Finnish (NFE) AF: 0.0609 AC: 34694 AN: 569672

Other (OTH) AF: 0.0792 AC: 2239 AN: 28264

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000642 AC: 94 AN: 146464 Hom.: 0 Cov.: 32 AF XY: 0.000800 AC XY: 57 AN XY: 71286

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000499 AC: 20 AN: 40044

American (AMR) AF: 0.00198 AC: 29 AN: 14670

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 1 AN: 3396

East Asian (EAS) AF: 0.000787 AC: 4 AN: 5080

South Asian (SAS) AF: 0.00 AC: 0 AN: 4622

European-Finnish (FIN) AF: 0.00182 AC: 17 AN: 9356

Middle Eastern (MID) AF: 0.00357 AC: 1 AN: 280

European-Non Finnish (NFE) AF: 0.000318 AC: 21 AN: 66104

Other (OTH) AF: 0.000497 AC: 1 AN: 2012

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0510 Hom.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.052
Mutation Taster		=100/0	polymorphism

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: rs3214646; hg19: chr6-138192324; COSMIC: COSV52800134; COSMIC: COSV52800134;