6-137881241-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001270508.2(TNFAIP3):c.2295C>T(p.Pro765Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00482 in 1,601,274 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 158 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 139 hom. )

Consequence

TNFAIP3
NM_001270508.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.25

Publications

11 publications found

Variant links:

COSMIC-nc: COSV52797472

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

TNFAIP3 links:

ENSG00000287393 (HGNC:):

ENSG00000287393 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 6-137881241-C-T is Benign according to our data. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137881241-C-T is described in CliVar as Benign. Clinvar id is 776164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2 link	c.2295C>T	p.Pro765Pro	synonymous_variant	Exon 9 of 9	ENST00000612899.5	NP_001257437.1	P21580

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5 link	c.2295C>T	p.Pro765Pro	synonymous_variant	Exon 9 of 9	5	NM_001270508.2	ENSP00000481570.1		P21580

Frequencies

GnomAD3 genomes

AF:

0.0268

AC:

4067

AN:

151914

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0912

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0283

GnomAD2 exomes

AF:

0.00655

AC:

1566

AN:

239118

AF XY:

0.00466

show subpopulations

Gnomad AFR exome

AF:

0.0896

Gnomad AMR exome

AF:

0.00469

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000566

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000165

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00251

AC:

3640

AN:

1449242

Hom.:

139

Cov.:

AF XY:

0.00212

AC XY:

1530

AN XY:

720352

show subpopulations

African (AFR)

AF:

0.0871

AC:

2866

AN:

32886

American (AMR)

AF:

0.00576

AC:

241

AN:

41810

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25368

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39454

South Asian (SAS)

AF:

0.000141

AC:

AN:

85290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52938

Middle Eastern (MID)

AF:

0.00263

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.000145

AC:

160

AN:

1106020

Other (OTH)

AF:

0.00577

AC:

345

AN:

59764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

214

429

643

858

1072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0268

AC:

4072

AN:

152032

Hom.:

158

Cov.:

AF XY:

0.0261

AC XY:

1940

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0910

AC:

3772

AN:

41434

American (AMR)

AF:

0.0137

AC:

210

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

67986

Other (OTH)

AF:

0.0280

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

189

379

568

758

947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0144

Hom.:

Bravo

AF:

0.0309

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 06, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autoinflammatory syndrome, familial, Behcet-like 1

Benign:1

Sep 03, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

-0.61

CADD

Benign

0.12

(source)

DANN

Benign

0.73

PhyloP100

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over