rs140610274

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001270508.2(TNFAIP3):c.2036T>C(p.Ile679Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TNFAIP3
NM_001270508.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1O:1

Conservation

PhyloP100: 5.66

Publications

6 publications found

Variant links:

COSMIC-nc: COSV52803619

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: PanelApp Australia, Labcorp Genetics (formerly Invitae)
hereditary pediatric Behçet-like disease
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
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 -9 ACMG points.

BP6

Variant 6-137880200-T-C is Benign according to our data. Variant chr6-137880200-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 135346.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000138 (21/152162) while in subpopulation SAS AF = 0.000208 (1/4816). AF 95% confidence interval is 0.000102. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 21 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270508.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFAIP3	NM_001270508.2	MANE Select	c.2036T>C	p.Ile679Thr	missense	Exon 8 of 9	NP_001257437.1	P21580
TNFAIP3	NM_001270507.2		c.2036T>C	p.Ile679Thr	missense	Exon 8 of 9	NP_001257436.1	P21580
TNFAIP3	NM_006290.4		c.2036T>C	p.Ile679Thr	missense	Exon 8 of 9	NP_006281.1	P21580

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFAIP3	ENST00000612899.5	TSL:5 MANE Select	c.2036T>C	p.Ile679Thr	missense	Exon 8 of 9	ENSP00000481570.1	P21580
TNFAIP3	ENST00000237289.8	TSL:1	c.2036T>C	p.Ile679Thr	missense	Exon 8 of 9	ENSP00000237289.4	P21580
TNFAIP3	ENST00000420009.6	TSL:3	c.2036T>C	p.Ile679Thr	missense	Exon 8 of 9	ENSP00000401562.2	P21580

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000994

AC:

AN:

251492

AF XY:

0.0000883

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000109

AC:

159

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000990

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.000134

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000123

AC:

137

AN:

1112008

Other (OTH)

AF:

0.0000497

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000138

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41440

American (AMR)

AF:

0.000131

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000325

Hom.:

Bravo

AF:

0.000125

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

5.7

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.56

REVEL

Benign

0.21

Sift

Uncertain

0.011

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.69

MVP

0.36

MPC

1.1

ClinPred

0.38

GERP RS

6.1

Varity_R

0.19

gMVP

0.52

Mutation Taster

=59/41

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over