Variant chr6-137881241-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

Variant links:

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 links:

TNFAIP3 (HGNC:):

TNFAIP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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/exons	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2 linkuse as main transcript	c.2295C>T	p.Pro765Pro	synonymous_variant	9/9	ENST00000612899.5	NP_001257437.1	P21580

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5 linkuse as main transcript	c.2295C>T	p.Pro765Pro	synonymous_variant	9/9	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

GnomAD3 exomes

AF:

0.00655

AC:

1566

AN:

239118

Hom.:

AF XY:

0.00466

AC XY:

607

AN XY:

130240

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 SAS exome

AF:

0.000169

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

Gnomad4 AFR exome

AF:

0.0871

Gnomad4 AMR exome

AF:

0.00576

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000141

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000145

Gnomad4 OTH exome

AF:

0.00577

GnomAD4 genome

AF:

0.0268

AC:

4072

AN:

152032

Hom.:

158

Cov.:

AF XY:

0.0261

AC XY:

1940

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0910

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0280

Alfa

AF:

0.0154

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2021	- -

Autoinflammatory syndrome, familial, Behcet-like

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

May 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.12

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over