6-137876192-C-T

Variant names:

• chr6-137876192-C-T
• rs5029948
• NM_001270508.2:c.805+26C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001270508.2(TNFAIP3):​c.805+26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 1,590,148 control chromosomes in the GnomAD database, including 2,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (376 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1912 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0420
• Publications: 10 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

ENSG00000287393 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-137876192-C-T is Benign according to our data. Variant chr6-137876192-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.805+26C>T		intron_variant	Intron 5 of 8	ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.805+26C>T		intron_variant	Intron 5 of 8	5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9254 AN: 152202 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.00613

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0587

GnomAD2 exomes AF: 0.0429 AC: 10311 AN: 240434 AF XY: 0.0427

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.0288

Gnomad ASJ exome AF: 0.0733

Gnomad EAS exome AF: 0.000897

Gnomad FIN exome AF: 0.00787

Gnomad NFE exome AF: 0.0483

Gnomad OTH exome AF: 0.0477

GnomAD4 exome AF: 0.0469 AC: 67450 AN: 1437830 Hom.: 1912 Cov.: 27 AF XY: 0.0469 AC XY: 33573 AN XY: 715516

African (AFR) AF: 0.108 AC: 3522 AN: 32488

American (AMR) AF: 0.0307 AC: 1282 AN: 41762

Ashkenazi Jewish (ASJ) AF: 0.0756 AC: 1919 AN: 25394

East Asian (EAS) AF: 0.000658 AC: 26 AN: 39512

South Asian (SAS) AF: 0.0452 AC: 3751 AN: 83032

European-Finnish (FIN) AF: 0.00913 AC: 486 AN: 53238

Middle Eastern (MID) AF: 0.0835 AC: 476 AN: 5698

European-Non Finnish (NFE) AF: 0.0481 AC: 52809 AN: 1097216

Other (OTH) AF: 0.0534 AC: 3179 AN: 59490

GnomAD4 genome AF: 0.0609 AC: 9275 AN: 152318 Hom.: 376 Cov.: 32 AF XY: 0.0575 AC XY: 4281 AN XY: 74482

African (AFR) AF: 0.108 AC: 4506 AN: 41560

American (AMR) AF: 0.0474 AC: 725 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5192

South Asian (SAS) AF: 0.0391 AC: 189 AN: 4834

European-Finnish (FIN) AF: 0.00613 AC: 65 AN: 10608

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0482 AC: 3280 AN: 68028

Other (OTH) AF: 0.0624 AC: 132 AN: 2116

Alfa AF: 0.0568 Hom.: 130

Bravo AF: 0.0659

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.24
PhyloP100		-0.042
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: rs5029948; hg19: chr6-138197329; COSMIC: COSV52797703; COSMIC: COSV52797703;